SOURCES AND EFFECTS
OF IONIZING RADIATION
United Nations Scientific Committee on the Effectsof Atomic Radiation
UNSCEAR 1994 Report to the General Assembly,
with Scientific Annexes

UNITED NATIONSNew York, 1994

NOTE
The report of the Committee without its annexcs appears as Official Records of the
Gencral Assembly, Forty-ninth Session, Supplemerlt No. 46 (A/49/46).
The designation employed and the presentation of material in this publication do not imply
the expression of any opinion whalsoever on the part of the Secretariat of thc United Nations
concerning the legal status of any country, territory, city or area, or of its authorities, or concerningh e delimitation of its frontiers or boundaries.
The country names used in this docurnent are, in most cases, those that were in use at thetime the data were collected or the lext prepared. In other cases, however, the names have been
updated, where this was possible and appropriate, to reflect political changes.

UNITED NATIONS PUBLICATION
Sales No. E.94.IX.11
ISBN 92-1- 142211-6

ANNEX A
Epidemiological studies of radiation carcinogenesis

CONTENTSPage

INTRODUCTIONI.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

METHODOLOGICAL CONSIDERATIONS . . . . . . . . . . . . . . . . . . . 13
A THE ROLE AND LIMITATIONS OF EPIDEMIOLOGY . . . . . . . 13
B QUALITY OF DATA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
C. METHODS OF DATA ANALYSIS . . . . . . . . . . . . . . . . . . . . . . . 19
D SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23.
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IT. CARCINOGENIC EFFECTS OF EXTERNAL LOW-LET RADIATIONEXPOSURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
A. HIGH-DOSE-RATE EXPOSURES . . . . . . . . . . . . . . . . . . . . . . . . 24
1. Mortality and incidence in the life span study . . . . . . . . . . . . . 23
2. Site-specific cancer risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3. Differences by sex and by ethnic origin . . . . . . . . . . . . . . . . . 34
4. Effect of age at exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
5. Prenatal exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
6 Telnporal pattern of radiation-induced risk . . . . . . . . . . . . . . . 37
7 Dose response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
8. Fractionation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
9. Joint effects of radiation and other agents . . . . . . . . . . . . . . . . 45
10. Liletime risk estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
11. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
B LOW-DOSE-RATE EXPOSURES
52
1 Occupational studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2. Exposure to natural background radiation . . . . . . . . . . . . . . . . 57
3. Exposures from environ~~~ental
releases . . . . . . . . . . . . . . . . . . 58
4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

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III. CARCINOGENIC EFFECTS OF INTERNAL RADIATION EXPOSURES 60
A. LOW-LET RADIATION EXPOSURES . . . . . . . . . . . . . . . . . . . . . 60
1 Iodine.131 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
2. Other radionuclides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3. Global fallout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64.
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UNSCE4R 1994 REPORT

12

Page

B. HIGH-LET RADIATION EXPOSURES OTHER THAN RADON . .
1. Radium-224.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Radium-226 and radium-228 . . . . . . . . . . . . . . . . . . . . . . . . .
3. Thorium . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .
4. Plutoniunl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5. Uranium .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . .

6. Polonium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7. Sunlnlary . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RADON . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.. . . . .. . ..
1. Occupational exposures . . . . . . . . . . . . .
. . . . . . . . . ..
2. Effect of exposure rate . . . . . . . . . . .
3. Other issues: cigarette smoking, arsenic and cancer at other sites. . . . ..
4. Residential exposures . . . . . . . . . . . . . . . . .
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5. Surnmary . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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IV. OTHER RELEVANT STUDIES OF CARCINOGENIC EFFECTS . . . . . 82
A. CANCER NEAR NUCLEAR INSTALLATIONS . . . . . . . . . . . . . . 82
B. PARTICIPANTS IN ATMOSPHERICNUCLEAR WEAPONS TESTS . . . . . . . . . . . . . . . . . . . . . . . . . . 85
C. SENSITIVE SUBGROUPS OF THE POPULATION . . . . . . . . . . . 87
CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Figures . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Glossary . . . . . . . . . .
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. . . . . 164. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
References . . . . . . .

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INTRODUCTION
1. Thc results of epidemiological investigations form
the main basis for quantifying the risks of cancer induction
in man following exposure to ionizing radiation. Manysuch studies have been completed and published and rnanyothers are in progress to evaluate the effects of irradiationin groups of individuals cxposcd inadvertently as a resultof conditions in the workplace, at home or in tl~eermironment or because of atomic detonations or intentionally for
purposes of diagnosing or treating diseases.

2 In the UNSCEAR 1988 Report [U2] the results of
epidenliological studies were examined to derive estiniatcsof the risk of cancer induction from exposures to ionizing
radiation. The estimates were based primarily on theextended follow-up wit11 revised dosimetry or the lire spanstudy of survivors of the atornic bombings of Hiroshima
and Nagasaki. The risk estimates for cancer referred specifically to the Japanese population exposed to absorbed
doses of the order oC 1 Gy of uniform whole-body low-

LET radiation at high dose ratc. The results of otherstudies were used primarily to support the principal results
derived from the life span study.
3. In this Annex further review of epidenliologicalstudics of radiation carcinogenesis is provided. One
objective is to review the risk estimates in the UNSCEAR
1988 Report and assess their validity in the light of new
information on all epidemiological sources. Further studiesof the survivors of the atomic bonibings in Japan provide
new it~formationon cancer incidence, niortality, doseresponse relationships, h e effects of expasure in childhoodand the appropriateness of various models of radiation risk
for use in risk projection. A large number of additional
epidemiological studies are contributing quantitative orotherwise useful information on the effects of both highand low-LET ionizing radiation in human populations.
They include studies of patie~~ts
exposed to radiation for
diagnostic or therapeutic puyoses, studies of workers

ANNFX A: EPIDEMIOI-OGICALSTUDIES OF TZADIATION CARCINOGENESIS

occupationally exposed in the nuclear industry, studies of
populations exposed to terrestrial gamma rays at varying
levels and to othcr environmental exposures, studies ofhidividuals exposed to radon in homes and othcr buildings.
and studies of the effects of local and global fallout fromatmospheric tests of nuclcar weapons.

4. Although it has been well established that radiation
exposure after high doses causes an increased risk ofcancer in many organs, there remain many importantquestions about the effects of high-dose and high-dose-rate
exposure compared to the effects of low-dose chronic
exposures; variation in risk with age at exposure, individual sensitivity and cthnicity, including transferral of risk
fiom one population to another, changes in dose responsewith tune since exposure; and the joint effects of radiationand othcr agents. As epidemiological data accuniulatc, it
is possible to carry out more detailed investigations ofthese issues. Recent findings arc reviewed in this Aru~ex.

13

The data available fro111 epidemiological studies
5.
allow estimate. of radiation risk to be calculated. While itwould be desirable to make joint analyses of all these data.
difkrences in quality and lack of sufficient information in
many of the studies present great difficulties. The Comrnittcc has, however, attempted to make a comparative
study of risk esti~natesfor specific types of cancer that canbe separately derived from the various studies. The types
or sites of cancer considered here include those for whichdata are available fiom one or more studies involving
reasonably large populations with quantitativc individualor population average dose estimates. These risk estimatesshould be interprelcd cautiously because of differences
between the various study populations, but they nevertheless provide a rough guide to the degree of consistency
among the various studics. As an aid in the interpretationof the risk estimates derived here, descriptions arc provided of the nature of the various populations considered
and of the strengths and linlitations of thcse studies.

I. M~HODOLOGTCALCONSIDERATIONS
A. TEE ROLE AND LIMITATIONSOF EPIDEMIOLOGY
6. Among the biological effects of concern whenhuman beings are exposed to low doses of ionizing radiation, the most uiiporlant long-tern1 effect is the possible
induction of cancer. Much can be learned about the natureof the cancer-induction process from laboratory expenmcnls in cellular systems and animals. Even some insights
into the mechanism of induction may be obtained in thisway. Nevertheless, until now the most potent method ofstudying radiation-induced cancer is the epidemiologicalstudy of exposed human populations. Only epidemiology
is able to describe the types of cancer induced in humans,
their frequency as a function of dose and time after
exposure and the many factors, such as age and sex, thatmodify their expression. Furthemlore, only epidemiology
is able to quantify these responses and, as a result, derive
estimates of the risks of cancer induction as a function ofdose. As successful as epidemiology has been in contributing to a broad understanding of radiation-inducedtun-~oursin humans and the quantitative risks of h e
p r o a s , i has some inherent Ihnitations. When the dose
is high, epidemiological studies have identified clear-cut
responses, and risk estixnatcs for many types of cancer
have been derived and heir dependencies on ohcr factors
explored. However, when the dose is low and the effect tobc deleclcd is vcry small compared with the natural
occurrence of cancer in the irradiated population, quantification of the risks is vcry difficult and perhaps
impossible. Additional strengths arid weaknesses of
epidcmiology will be discussed further below.

7. Epidemiological studies can provide valuable
infonilation about the applicability to humans of dose
response and other information sugysted by data obtainedin experi~ncnlalsystems. Although epidemiology is not
intrinsically expected to conlribute much to the overall
knowledge of radiobiological mechanisms, the manypara~netersthat epiden~iologyhas established as modifying
and influencing cancer induction must nevertheless betaken into account in any theory of the mechanisms ofaction of radiation-induced cancer. Radiation epidemiology
has already contributed to general theories of carcinogenesis, as, for example, in breast cancer, where epidcmiological studies have shown that at young ages the female
breast is especially vulnerable to enviro~unenlalinsult.
Some information on the carcinogenic effccls of
8.
radiation exposure is provided by clinical trials, but mostepidemiological studies of radiation effects are inherently
observational in nature. That is, they are arranged by circumstance rather than as a result of experimental design.
This means that the conditions of exposure, the study
population and the allocation of individuals to the various
exposure levels are outside the control of I11c rcscarchworker. In fact, the exposures are often determined forreasons quite unconnected with the objectives of a particular epidemiological study. In the case of exposure toionizing radiation, exposures occur, for example, as aresult of the geographic location of an individual at aparticular time (in studies of the survivor; of the atomic
bombings in Japan); the place of residence and type ofdwelling (in studies of the effects of domestic exposure toradon and of exposure to terrestrial gamma-radiation);

14

UNSCEAR 1994 REPORT

occupation (in studies of radium dial painters, uranium
miners, tin miners and workers in the nuclear industry);
medical treatment of discasc (in studies of patients withankylosing spondylitis or cervical cancer); or simply prevalent ~nedicalfashion (in studies of cliildren who received
radiotherapy for a supposedly e~ilargcd thymus andchildren whose mothers were given x-ray examinations
during pregnancy).
The characteristics of epidemiological studics havethe following conseque~~ces:

9.

(a)

@)

(c)

the effects of interest cannot always be studied
directly or with the desired precision;
randomkation procedures can rarely be used toensure the absence of undesirable systematic differences between those exposed at different levels;
studies cannot usually be repeated at the commandof the investigator.

The obse~ationsUiat can bc made are limited to theeffects of exposures that have actually occurred. For
example, while Ihc effect of radon exposure on lungcancer incidence in the general population is of greatinteres4 currcnt risk cstirnatcs are deterniincd only instudies of niiners wilt1 occupational exposures to radonand its decay products. These populations consist of males
who were bctwcc~~
the ages of 18 and 65 at the tinie of
exposure, and UIC conditions under which the exposures
were received differ lnarkcdly from those in which general
population cxlmsurcs arc rcccived. In addition, there areoften systcniatic diffcrcnccs bctwccn those exposed at
different levels and the general population; appropriatecomparison populations arc therefore important. For
example, in the thyrotoxicosis study carried out in thc
United States [S2], an excess of leukaemia was observed
when rates for patients treated with 1 3 1 were~compared torates for the gencral population. However, a non-exposedgroup of thyrotoxicosis patients was found to have leukaemia risks coniparable to the patients treated with I3l1.

10. Because investigators lack control over many
important aspects of epidcrniological studies, observed
associationsbetween exposure and subsequent disease canbe distorted by the presence of factors associated with theexposure and with the disease in the individuals studied.
Thus, an imporhnt aspect of the design and analysis ofany epidemiological study is to identify and eliniinate such
distortions. Factors such as age, sex and cthnicity arc
important, easily mcasurcd dctcrniiiants of disease thatshould be taken into account in virtually every study
wortby of serious corsidcration. OUier factors, such as
cigarette smoking, socio-economic status and eniploynienthistory, arc quantifiable ill principle if accurate records areavailable or if ir~tervicwscan be carried out with eachstudy participant. Whco such infonilation is obtailied after
the exposure or discasc diagnosis, special care must be
taken to ensure that the ascertainment is of equal quality
for exposed and unexposed individuals or for cases andcontrols.

11. A common study design in radiation epidemiology
is the cohort study. I11 a cohort study, a fixed, well-definedgroup of individuals not known to be suffering from thedisease, or diseases, of interest is enrolled and followed
forward in time. Infornlation is collected on deaths h m ,and if possible, incidences of the diseases of interest in theenrolled population. Because the diseases of interest areoften rare and the effects of exposure relatively small andbecause there is a need to determine how risks vary with
sex, age at exposure, time or other factors, epideniiologicalcohort studies of radiation effects need to include
thousands or even tens of thousands of individuals in the
study group, and follow-up must coritinuc for years or
decades. Although prospective follow-up data are available
in many cases, most cohort studies were b e y n with aretrospective review of historical data such as employment
or medical treatment records. The size of a cohort study
and, for a retrospective cohort study, its timing usually
preclude pcrsonal contact between the investigators andindividual cohort rnenibcrs. Thus, individual data on otherthan a few basic items are rarely available. An importantelement in the design of cohort studies is to ensure that therelationship between disease rates and the exposure is not
distorted by unnieasurcd factors.
if a specific
12. It is not possible at prc.scnt to detem~ir~ecancer was caused by radiation, although there areencouraging indications that advan- in molecular biology
will allow such a dctcnninatio~~
IT16, Ul]. Therefore, tlle
extent of radiation-induced cancer in a coliort must be
inferred by comparing si~iiilarkmups with diffcrcnt lcvcisof exposure. In cohort studies this rnay involve the comparison of exposed and unexposed gmups or, ideally,groups receiving a range of exposures. In many studies ofradiation effects it is not possible to include an unexposed
control group; therefore, inferences arc based on comparison of the observed number of cascs to an expected
number derived h n i national or regional rates. Whilethese rates arc usually rcadily available for mortality, they
are much lcss often available for cancer incidence. Thus,
an intenial comparison g o u p is especially important forstudies of radiation-induced cancer incidence, as illush-atedby the thyrotoxicosis study mentioned above. Whennational or regional rates niust be used, it is desirable toinvestigate, if possible, the validity of the comparison. Thiswas done in the British ankylosing spondylitis study byidentifying and followirg up roughly 1,000 individuals
with the disease who were not treated with radiation [S21].
When internal controls are avi~ilablc,national rates may
still be useful as a check on the validity of the control
group and on the stability of infercnccs about dose effects.
This has been done in some an;ilyses of data on survivorsof the atomic bombings in Japan [P13, P231.

13. When it is not pasihlc or practicable to conduct acohort study, case-control studics can providc valuable
infornlation on radiation effects. The strcngth of a casecontrol study lies in its ability to niake effective use of

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

data on relatively small numbers of cases and controls. In
this type of study, information is collected both onindividuals who have already developed the disease and on
disease-flee controls. Controls are usually individuallymatched to the cases with regard to age, sex and otherrelevant factors. Case-control studies are often constructed
hom within previously defined cohorts in order to allow
the use of more detailed data than could be obtained forthe full cohort. In a case-control study, inference is basedon a comparison of the level of various hctors, e.g.
radiation dose, in the cases and controls. The validity of acase-control study depends on the extent to which thecontrols are truly representative of the population fromwhich the cases were drawn. This is not always easy toachieve. Case-control studies are appropriate for gaining
insights into several areas in radiation epidemiology.
Examples include the assessment of the effect of radon
exposure in the home on lung cancer risk among pcoplewith different smoking habits [B37, P30, S5] and of theinteractions of radiation and other risk factors for breast
cancer in the survivors of the atomic bombings in Japan[L16] and cervical cancer patients [B20,B211.
14. An important consequence of the observational
nature of epidemiology is that considerable caution must
be exercised before assuming that the rela tionship between
a disease and some environnlental or occupational
exposure is a causal one. Once the requirements for highquality data and appropriate analysis have been satisfied,critcria for evaluating causality include the following: Blestrength of the association between the disease end-point
and the presumed causative factor; the consistency of datafrom a variety of studies; the existence of a dose-response
gradient; and experinicntal evidence that similar effects
can be produced in the laboratory. In the context ofradiation, a good example is given by lung cancer andoccupational exposure to radon [C6]. In the late nineteenth
and early twentieth centuries, radon concentrations in themines of central Europe were high, and it was eventually
established that approximately 50% of the miners diedfrom lung cancer p14]. Elevated risks of lung cancer
were latcr seen in a variety of other mining populations
exposed to high concentrations of radon, including minersof iron ore in Sweden and Britain, fluorspar miners in
Canada and uranium miners in Canada and the UnitedStates. A very recent analysis of 11 underground minerstudies indicates that of almost 2,700 lung cancers foundamong 68,000 miners, fully 40% are atiriiutable to radon
exposure during the miners' w o r m lives [L21]. Also,
some of the more detailed studies have demonstrated astrong dose-response relationship, and similar results inlaboratory studies on rats and dogs have been available
since the 1970s. Doubts about the causality of the relation
are reduced by the observation that miners in other typesof mines, such as coal or nickel miners, which would havebccn equally dusty but where levels of radon are notincreased, have been shown to have little or no increase in
the risk of lung cancer or possibly even a deacase [A4,15

G12, M14,M161. Despite these Endings, the role of dusty
conditions in the mines and especially the presence ofarsenic are not yet hlly understood [C21,L171.
15. Radiation exposures of the general population
usually involve low doses delivered gradually over time.
For example, in the UNSCEAR 1993 Report [Ul], it wasestimated that the average annual effective dose to adults
hom all natural sources of radiation is about 2 mSv andthat the proportion of pcople receiving an annual effective
dose in excess of 10 mSv is very low. Interest in assessing
the effects of radiation for the purposes of radiologicalprotection therefore centres on the effects of expasures toa few rnillisievert per year. The vast sample sizes thatwould be required for direct study of the effects of such
exposures were discussed by Land p7] and by G a s[G24]. That it is difficult for epidemiological studies toprovide definitive results in such circumstances becomes
evident.

16. The ability of radiation to act as a carcinogen in
most organs and tissues of the body has been wellestablished by studies at much higher doses (for example,
of about 1 Sv or more, often delivered at a hlgh dose rate)and in which the exposure has increased cancer morbidity
rates by 40%-50% or more, i.e. studies in which therelative risk is about 1.5. As the results of numerous
studies discussed in this Annex illustrate, epideniiologicalstudies can detect and quantify effects of this magnitude
and provide useful information on the factom that affectthem, including sex and age at exposure. However, if astudy is to address lower dose exposures (0.1 Sv or less),and if it is assumed that the response is linear in dose, theincrease in cancer risks would be only 5% or less, i.e. therelative risk would be 1.05 or less. To have a reasonableprobability of detecting a risk (i.e. statistical power) of thismagnitude, an epidemiological study would require
thousands or even hundreds of thousands of cases of thedisease of interest among exposed subjects. Even if it werefeasible to assemble cohorts (or case series) large enoughto detect such low-dose effects, it would be difficult tointerpret any fmdings because other undetected small
differences between the control and exposed populations
would easily mask existing effects or induce spurious
effects of this size. In view of the lack of power of moststudies to detect low-dose effects, it should be recognizedthat the failure of a particular study to denionstrate aneffect (positive or negative) at low doses is not necessady
an indication that such effects do not exist Furthemlore,
the fact that epidemiological studies lack the power todetect the small effects that might be seen at low doses
does riot mean that they provide no information on lowdose effects. Such studies can often provide upper lirnits
Cor the magnitude of the risk. Also, it is imporlant to notcthat epidemiological studies have been quite successful indetecting the effects of radiation exposure in sensitivesubgroups of the population, e.g. prenatal exposure to x
rays with exposures of about 0.01 Gy and childhood
thyroid cancer at doses of roughly 0.1 Gy.

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UNSCMR 1994 REPORT

17. The tern1 "statistical powern is relevant to the issueof significantresults from radiation studies, especially lowdose studies. Statistical power depends on the sample size,
the length of follow-up, the method of analysis and theaverage dose to which the group is exposed. The followup niust extend for a substantial period beyond the latency
period, which is the time between the exposure and theoccurrence of disease. When doses are low ( ~ 0 . 2Sv), thesample size muyt be very large in order to detect a small
effect, as noted above [G24, L7].
18. It would seem that, for the foreseeable future, theimportant questions in epidemiology - the effect of
hactionated low-dose exposures, the temporal pattent of
the effect in a population, the relative magnitude of theeffect among those exposed at different ages and the joint
effect of radiation and other agents - must continue to beevaluated fiom studies on effects at high dose$, withsupporting laboratory experiments to guide the extrapolation from high to low doses. Nevertheless, it isessential that human populations exposed at lower doses
be monitored to ensure that extrapolation frorti the resultsof studies on effects at high doses has not given risk
estimates that are inappropriate. The most suitable groups
for study in this way are those in which some individuals
have exposures higher than those received by mostmembers of the public from natural radiation or conlnlon
diagnostic medical procedures. Examples of such groups
irlclude radiation workers and people living in areas withhigh indoor radon concentrations. Studies of Ule geographical variation in mortality with exposure to sources
such as terrestrial gamma-radiation and radon are inprinciple also important. However, in practice it is diffi~vlt
to interpret such studies owing to problems in obtaining
adequate exposure data and in allowing for socio-economic and other factors that may influence disease ratcs toa greater extent than the variation in radiation expasures.

19. The interpretation of results from studies of populations exposed to low levels of radiation presents many
problems. Inevitably, the studies will tend to be negativein the sense that major potential effects, such as theassociation behveen exposure and leukaernia rates may notreach statistical significance. However, they may still be ofgreat value in so far as they provide upper bounds to therisk in situations of practical interest. Also, if several
similar studies can be carried out, as is at present happening with studies of radiation workers and residential radon
exposures, it may be possible to cornbine results, making
it easier to quantify an effect
20. There is still another cotlsequencc of studying
populations exposed to low levels of radiation: if a large
number of significance tests are carried out, some findings
will reach nonlinal statistical signif~cancz purely bychance. To minunize the difficulties of interpretation i nsuch situations, it is important to clearly specitjl which of
the many hypotheses tested were of special interest a

priori and which were singled out after the event For
example, in 1982 Smith and Doll [S13] reported a large,
statistically significant standardized mortality ratio (SMR)
for turnours o l the central nervous system other than thoseof the brain among British patients who received radiotherapy for ankylosing spondylitis. With additional followup, however, the magnitude of this risk estimate decreased
markedly, and the statistical significance of the effectdisappeared IDS]. Sindarly, earlier analyses reported
statistically sigmificant increased risks of multiple myelonla
in survivors of the atomic bombings [S7] and in workers
at the Hanford plant [G20]. However, in the life spanstudy incidence data [P33] in which roughly 50% morecases are reviewed, evidence for increased myeloma risks
in the cohort is weak and, in any case, the risk is likely to
be much smaller than suggested in the earlier reports. A
recent repott on the Hanford workers [GI61repofi lower
risks that are no longer statistically significant

21. The above discussion is formulated largely in tennsof ~nortalityand thus ignores the fact that some radiationinduced cancers are not fatal. The difference between
incidence and ~nortality is sometin~es small, as, forexample, in cancers at sites such as the stomach, liver orpancreas or in adult leukaemia, which have low (40%)
relative survival rates. (The relative survival rate is theratio of the probability of surviving for a fixed period,
usually five years, after diagnosis to the survival probability in the general population [J6].) However, mortality
data cannot be expected to provide complete or reliablerisk estinialcs for sites with high relative survival rates,
since such cancers are unlikely to be listed as the cause ofdeath. Examples of cancers that have relative survival ratcs
greater than 50% include thyroid, melanoma and nonmclanoma skin cancers. female breast, uterine corpus,
prostate and urinary bladder w29]. The issue of incidence
versus mortality is further complicated by the fact thatsurvival rates vary widely fiom country to counlry (seeTable 1) and by the fact that they vary with tune withinsingle countries for many reasons, including improvements
in n ~ d i c a therdpyl(see, for example, [HK)]).
22. Since many countries do not have general population
cancer registries and radiation-exposed populations are notusually hlcluded UI existing cancer registries, it is difficult
to carry out incidence studics of radiation effects. However, despite the difficulties a number of important
incidence studies are now available. These i~lcludethe
registry-based cervical cancer cohort and case-contml
studies [B12, B21], survey-based studies of breast cancer
arnong wornen exposed to radiation for the treatment or
diagnosis of various medical conditions [Bl. B18, B31,
M19, S9), analyses of breast cancer and, most recently, aseries of general analyses of cancer-registry-based incidence data on the survivors of the atomic bombings inJapan p33, T15]. As has been noted by Hoel and Dinse(H291, it is possible to construct models for cancer
incidence at some sites by combining data on ~nortality

ANNM A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

following radiation exposure with case-fatality data.
However, these methods appear to be of limited utility as
they require data on the time Gorn diagnosis to death.

23. Doll and Peto [Dl91 discussed other issues related
to the strengths and weaknesses of epidemiological studies.
By the nature of epidemiological studies, the contributionof any single study, however excellent, is much more
limited than that of an experimental study. Firm conclusions can be drawn only when a number of studies
canied out in difl-erent circumstances provide similar
results. Accordingly, it is espccially iniportant in this fieldto carry out critical reviews of all the relevant studies fromtime to time, and to attempt to integrate the available
information into a meaningful composite.

B. QUALITY OF DATA
24. Careful attention to data quality is iniportant in the
conduct, intcrprctation and comparison of epidemiologicalstudies. There are many hctors that can affect the qualityof the data in studies of populations exposed to radiation.
These include inconiplete follow-up or exposure-relateddiffcrcnccs in the coniplehless of follow-up; recall bias in
the ascertainrncnt of exposure information; and comparability of the exposed and control groups. In addition, whenmoving beyond simple ascertainment of the existence ofan effect to morc prccisc quantit~tivedescriptions of theeffect, there must be a good understanding of Ille natureand quality of the dosimetric data. In co~nparingthe resultsof difircnt studies or in applying risks from one population to another, hl addition to all these hctors that might
affect the data quality, it is necessary to consider carefully
other factors, such as {hecomparability of the populations
under consideration witll respect to age, sex, ethnicity,
smoking, diet and possible specific demographic factors.

25. In cohort studies it is essential either to ensure thatthe follow-up is virtually complete and that all relevant
occurrences of disease in the enrolled population havebeen identified or to understand the nature of incomplete
follow-up and adjust for it. It is particularly important toobtain and make use of information on niigation or loss
to follow-up. Obtaining coriiplcte rollow-up is generally
much easier for momlity data than for incidence data. For
example, in Japan the conlpulsory system of family
registration (kmeki) makes it possible to obtain deathcerliticatcs for virtually all dcccased mernbers of theatomic bomb survivor cohort, while canccr incidcnce data
are generally available o~llyfor survivors who reside in theareas covered by the Hiroshima and Nagasaki tuniour
registries at the tinie of diagnosis. In mortality analyses,
koseki information on cnligration Goni Japan is available
and is used to identify people who are lost to follow-up.
As will be described later, special measures were taken to
allow for the effects of migation in analyses of the dataon cancer incidence in Ihc survivors of the atomic bomb-

17

ings. In some places (e.g. the Nordic counlries), longstanding national cancer i~~cidcnce
registries exist, andcancer ascertainment is facilitated by record linkage
procedures based on personal identification numbers.

26. Even when good sources of follow-up data are
available, one must be concerned about the quality of thedata and their interpretation. For exaniple, the general
underreporting of cancer on death certificates, which may
be age-dependent, means that although reasonableestimates can be made of relative risks, absolute risks areunderestimated from dead1 certificate diagnoses. In sitespecific analyses, especially those based on deathcertificates, the misclassification of canccr types on thedeath certificate (mainly undemporting of cancer) can also
affect risk estimates. Sposto ct al. [S66] investigated theimpact of cancerhon-cancer niisclassification and foundthat after allowing for cancer recorded as non-cancer andvice versa,cancer risk estiniates from the life span study
should be increased by more than 10% relative toestimates that ignore the effect of these recording errors.
27. Another concern in the conduct of epidemiologicalstudies involves the cornparability of the exposed andcontrol groups. This is particularly important when an
exposed population rate is co~nparcdto general population
rates, in which case the availability of valid appropriate
population rates is critical. The so-called "healthy workert'
effect [H44], in which workcrs tend to have lower
mortality rates for cancer and for otlier diseases Ihan thegeneral population especially in the lirst few years after
selection for employment, is one illustration of thisproblem. The healthy worker effect i$only one aspect of
the general problem of comparability of rates in any
selected cohort to rates for a general population. Causespe&c death or incidence rates can also exhibit g a tvariability within the general population for reasons otherstatus. Thus, when making comparisons
than e~nploy~nentto general population rates it is important, wheneverpossible, to emphasize relative risks and trend tests rather
than to focus simply on standardized mortality ratios. Even
if an unexposed internal comparison group is available,
there must bc concert1 for the appropriateness of thecomparisons being made and any unusual features of thecontrol population.

28.

It is also essential to avoid bias due to differing
probabilities of disease or to diffcrulg exposure detection
between exposed and unexposed individuals. Detection
bias can be a serious probleni for some outcomes (if, forexample, surveillance is increased as a rcsult of concern
about radiation exposures). As a result, many occult casesthat would olherwise go u~ldetectedmay be diagnosed, asof thyroid cancer
happens, for example, hi the detcctio~~with enhanced screening proccdurcs.
29. Another concern iivolvcs biases rcsulting Goni
exposures that may have Liken place becaisc of symptonls

18

UNSCEAR 1994 REPORTof a subsequent disease or Goni differential recall of
exposure for cases and controls. As an cxa~npleof theformer, the elevated risk of neoplasms other than
leukaernia or colon caner seen in the first five years after
ueatlncrlt in the British ankylosing spondylitis study is
discounted by the auU~orsbccau~se"sonle of the tumours
presenting soon after treatment may have caused thesyniptoms that wcrc incorrectly ascribed to spondylitis"[D6].
The possibility of rccall bias was mised in criticismsof the initial studies of prenatal radiation: it was felt thatparents of cases might have been more likely to reportprenatal x-ray examinations than parents of controls.

30. The important issue of adequatc statistical power
was discussed in the preceding Section. Indeed, it is wellknoun that epidemiological studies are problematic whenthe effects being studied arc much less than half thenormal baselulc risk. Thus, increasing power by increasing
the sample size is unlikely to provide reliable estimates ofrisk at low doses and low effect levels, because of thepossible presence of competing or confounding risk factorsthat might safely be ignored at high doses and effectlevels. There may well be unknown factors that increaseor decrease risk by a few percentage points, i.e. near thelevel of effect in a low-dose study. Such Bctors will nothave come to attention earlier because they seldom if everare present at levels high enough to be apparent in an
exploratory study of modest size, and they might beconfounded wiUl cxposurc to low doses of radiation The
problem can be addrcsscd by increasing Ulc amount of
infomiation on cach study subjccl, but that solution can bevery expensive for a lagc study, and it would be guided
by very little prior infomiation.
31. A related qucstion concenls the influence of chancein statistical observations in studies in which multiple
comparisons are made. If, for example, tests of significanre are conducted at tl~e5 % level for a series of coniparisons between control and exposed groups, 5% (1 in20) of the tests will rcsult in an apparent difference due tochance alone. Thus, in a study involving many such comparisons (e.g. in a low-dose environmental study withmany different cancer end-points evaluated) erroneous
positive or negative results are likely to occur with afrequency that depends on the level of significance in the
tcst.

32. The Conimittce notcs that reliance on studies thathave dcmonstratcd slatistically significant effects can bemisleading. First, journals are rnore likely to publish (andaulhors niorc likely to report) studies that have somestatislically signilicant rcsull Secondly, point estimates ofrisks for statistically significant cIfccts are, especially forsmall studies, biascd upwiird and can be misleading if not
put in the conlcxt of olher results. In addition. since
epidemiological studies of radiation effects cannot usually
be designed to eraure adcquatc power to dctcct cffccts, theranges of risk estimates fro111pmitive and negative studies
can pmvidc useful information on risk.

33. In epiderniological studies of radiation effects,
suitable measurements of individual doses made at thetime of exposure arc usually unavailable. In such cases
estimates are developed by recon..tructing tl~eradiation
fields based on theoretical constructs or computationalmodels of the original exposures (e.g. the life span study)
or by carrying out post hoc mcasurcnienls for rcpresentarive exposures believed to be comparable to those that
accurred originally (e.g. the tinca capitis study in Israel).
Dose estimates niay be assigned to groups of subjects
believed to have been exposed under comparable conditions or, as was done for the ankylosiry spondylitis study
in the United Kingdom, individual dose estimates
computed for a sample of subjects may have been used toestimate population-average doses to selected organs.
These estimates were more accurate for some organs thanfor others. More precise estimates of organ dose werepossible in the cervical cancer study [B21] and in the
study of benign gynaecological disease PSI. Averageorgan doses must be used with caution when the nature of
the exposure varies widely between subjects. Even when
individual monitoring measurements are available, as forexample in many studies of nuclear workers, here areoften questions about adequacy and completeness, since
the data were collected for purposes other than the studyof radiation effects and niay not exactly suit the nwds ofan epidemiological study. Furthennore, the derivation oforgan doses from personal monitoring rncasurements is
subject to some unc~rtainticsowing to the nature of the
exposure and tile orientation of the individual in theradiation Geld.

34. In epidemiological studies whose sole aim is thc
simple identificatior~of an effect, such as cancer, with acausative agent, such as radiation, it can be suficient todistinguish between exposed and unexposed individuals,
i.e. a precise knowledge of individual exposure levels is
not critical. However, in niore quantitative studies, inwhich the goal is to provide an estimate of the doseresponse function, the quality of the dosimetric data is as
important as the quantity and quality of the data on theoutcome of interest
35. The impact of errors in dosimetry has been
examined most extensively for the data of the life spanstudy of survivors of the atorriic bombings. Jablon [Jl],who fmt considered this problem, cor~cludcdthat uncertainties in the data on location and shielding forindividual survivors would l a d to errors of 357&40% in
individual dose estimates p65D dosimetry system). Using
data on discrete sympton~ssuch ;IS cpilalion and blecdu~g,
Gilbert and Ohara [GlO] f011nd evidence of either syskmatic differences or differing arnounh of random error in
the methods used to construct the T65D dose estiniates.
Gilbert's results supported average crrors in individual
dose estimates comparable to those noted by Jablon.
Following revision of tl~edosimetry (to DS86) for theseveral,survivors of the atomic bo~nbingsin Japan [ W ]ANNEX A: EPIDEMIOLOGICAL STUDIESi OF RhDIATION CAKCINOGENESIS

studies have examined the nature of random errors inindividual dose estimates. Pierce et al. F 9 , P31] developed
methods to adjust risk estimates for the biases resulting
fiom random errors in individual dose estimates. They
concluded that random errors of 30%-40% can lead to risk
estimates for solid cancers that are 7%11% lower and risk
estimates for leukaemia that are 4%7% lower than theywould be if "en doses could be used in risk estimation
Thus, to correct for this effect, risk estimates would need
to be increased by those amounts. Sbam et al. [S22] foundthat for the same estimated doses epilation rates differedvery significantly by shielding category. Sposto et al.
[S55] compared chromosome aberration dose-response
curves for epilators and nonepilators and concluded that
40%50% random errors in individual DS86 dose
estimates would be needed to explain the observed stceper
slope seen for survivors who reported severe epilation

36. The studies just 11otcd have focused on random
errors in individual dose estimates and the impact of such
errors on risk estimates. They do not deal with possible
systematic errors in the DS86 dosimetry, such as thosedescribed by Straume et al. [SS6], which are discussed
later (paragraphs 156-158). The attention is given to theimpact of dose errors in the data on survivors of theatomic bombings does not imply that the dose estimates
are worse than those in other studies of radiation effects:
rather, it reflects the availability of a l a g e amount of dataon individual swivors and the concern of those involvedin the Japanese studies to provide a thorough summary of
the strengths and limitations of the data.
37. Tlie quality of the dosimetry has also been examined
for some other studies of radiation-exposed populations.
For example, in a study of the estimated radiation doses to
12 bone marrow sites arid various other organs of ankylosing spndylitis patients treated in the United Kingdom
with x rays, Lewis et al. p]coniparcd the mean marrowdoses obtained from the Monte Carlo calculations withthose obtained from experiments on a physical phantom.
Although the results obtained using the two methods werevery highly corrclatcd, the Monk Carlo estimates were, on
average, 19% higher. The most likely explanations for lhe
difCcrence are the different distributions of energics in the
prinlary photon beam and the different compositions ofbone niarrow used in the two studies. Thc results ofLewis
et al. suggest that the coefficient of variation, i.e. thestandard deviation divided by the mean, for individual
dose estimates ranges from 10% for organs close to thebeam to about 50% for less directly exposed organs. Morerecently, Stovall et al. [S18] descn'bed efforts toreconstruct doses for medical exposures. Dose estunatcs
developed by Stovall et al. are used hi a number of
epiden~iologicalstudies.
38. Better descriptions of the uncertainties in individual
dose estimates arc needed in most studies of radiation
effects. The fact that such issues are not addressed in the19presentation of results of a specific study should not betaken as an indication that the dose estimates are padcularly accurate or that uncertainties in individual dose
estimates would have a negligible impact on the reported
risk estimates.

C. MKIWODS OF DATA ANALYSIS
39. The analysis of epidemiological studies should
involve life-table methods to lit regmion models thattake into account sex- and age-specific death or incidence
rates and any other factors influencing disease incidence
that may be correlated with exposure and for which data
are available. Statistical methods were summarized by
Breslow and Day [B28, B291, and modelling issues in thecontext of epidemiological studies of radiation effects werediscussed by Preston p 3 2 ] and Vaeth [V12].
40. For the most part, the questions of interest in theanalysis of studies of the effects of radiation in persons
known to have been exposed to appreciable doses havegone beyond answering the basic question of whether
there is an association between exposure and disease.
Interest now centres on issues of a more complex nature,such as the magnitude and duration of any effects, and thevariation in risk among those exposed at different ages.
For many studies data are now available to address thesequestions, at least in part. However, correct inferences canbe made only if they are based on models that accuratelyreflect the variation in disease rates indicated by the data.
Tf inappropriate or oversimplified models are used, higldy
misleading inferences can be made. For example, when
the annual change in the excess relative risk of nonleukaemia cancer rtiortality aniong survivors of the atomic
bombings in Japan aRer 1%0 was calculated ignoring theeffect of age at exposure, the excess relative risk wasfound to be increasing at 3.5% per year. However, when
it was calculated adjusting for the effect of age at
exposure, the excess relative risk was found to be
decreasing slightly [S7].
41. 111 praenting the results of specific studies,
investigators usually focus on relalively simple descriptive
statistics or models of the experience of the study population. The results may average over or adjust for differences in the study population, such as age and sex, andmay include exIrapolation and projection to extend risk
estimates to lifetime experience. To ~nakeresults understandable alid to allow comparisons to be made with otherstudies, it is necessary to give some attention to thedefinition and use of the risk estimates.
42. Radiation effects are usually described in terms ofvarious siniple measures of the excess risk The mostconunonly used summary statistics are relative andabsolute risk estimates. In simple terms, if 0 is thenumber of events observed in a population and E is thenumber of events expected in the population in theabsence of exposure, the relative risk (RR) is defined as

and the excess risk (ER) is dcfi~~edasER = 0-E

PI

When comparing relative risks or presenting risks pcr unit
d m , as d w n i below, it is preferable to summariz.
results in terms of the e x e s rclativc risk (ERR), dcli~icdas

ERR = -0
-I
E

=-

0 -E
E

instead of the relative risk. In order to compare estimatesderived from populations with different levels of exposure,
it is useful to work with risk per unit dose, callcd risk
coefficients. Thus, if D is the average dose receivcd by an
exposed population, the linear excess relative risk
coefficient is defined as

ERR =

0 -E
ED

The term dose arid the symbol D are used in a general
sense to represent absorbed dose (in gray) or weighted
dose (in sievert) with neutron RBE = 10, for the atoniic
bomb survivors (see paragraph 64). Both quantities
determined in equations (3) and (4) are comnlor~lyreferred
to as excess relative risk, the context making clear the
distinction. To compute roughly comparable values for thee x m s risk in different studies it is necessary to consider
both the dose and the amount of follow-up time. This isoften done through the use of the excess absolute risk
(EAR) per unit dose and per unit ti~neat risk:

0 -E
EAR = PY D
where PY is the number of person-years of follow-up.
the43. A variety of methods are used for con~putil~g
expected numbcrs of cases used in the above definitions.
It is mrnnion practice in epidemiology to allow for theeffects of age, sex and other characteristics of the study
population when computing the expected numbcrs ofcases. Estimates that arc computed allowing for such
effects arc callcd adjusted risks. However, WIICII (ascurrent data on radiation effects suggest) excess risks varywith age at cxposure, sex or follow-up time, the summary
shtistics deCied above are weighted averages involvirig an
implicit weighting that depends on the composition of the
population, with the largest weight being given to groups
that have the largest- number of cases. This rnc;ils, forexample, that the risk estimates generally cited for the life
span study, which were used as the basis for niany
calculations in the UNSCEAR 1988 Report [U21, areheavily irfflucnced by h e expcricncc of the older survivors
and that, owing to Ulc nature of Uie study, risks for

pcrsorls exposed as young adults contribute relatively little.
When excess relative risks of cancers other than leukaemia
fioni the life span study are computed by averaging risk
estimates for a small number of groupirlgs of age at
exposure and sex using equal weights, the resulting excess
relative risks are about 50% jpater than thc usual ageaveraged estimate that gives the greatest weight to theolder ~nernbersof the cohort F3).Since the age-averaged
surnrriary risk estimates depend heavily on the demographics of the population on which they were based,
similarities or differences in such simple average risk
estimates should be interpreted with caution.
44. The most comrnoll approach to exploring variationin the risks of radiation-induced disease is to carry out
separate analyses of subsets of the full data set Examples
include analyses of subsets defined by sex, age at exposure or time since cxposure. In a subset analysis, a siniple
summary measure is computed, and separate tests of thenull hypothesis of no excess risk are carried out for eachsubset Such analyses tend to promote overreliance on significance tests and overir~terpretationof sanlpling e r r o ~ .
Modern analytical methods and software make it easy tocarry out generalized regression analyses that crnphasijlc
tests for heterogeneity in response functions, e.g. that
determine whether or not risks differ significantly by age
at exposure or sex and that estimate the size of thediKerences [P35].Thcsc neth hods can be usefully employedeven ut studies without individual d m estimates.

45. In many studies, excess cancer believed to be
associated with radiation is reported without regard todose, usually because of the poor quality of individual
dose estimates. Summarizing risks in this way complicates the comparison of results from different studies,
since such comparisons are of little use in understanding
the magnitude and nature of radiation risks. When
dosinietric data are available and linear risk estimates are
deemed to be appropriate, the risk per unit dose should be
prcscnted. When non-linear dose functions are used, theyshould be described clearly and accompal~icdby evidence
for a lack of fit of the linear model. Any presentation ofrisks should be accompanied by a clear indication of thenature and quality of the dose estimates used.

46. In considering the risk of radiation-induced cancer
projected in time, it is comnlon to make use of what areoften referred to as lifetime risk estimatcs. Several studies[PI 1, TI41 have examincd the definition, interpretation andpresentation of lifetime risk estimates. T h m principles canbe identified that underlie the cornputation of lifetime
risks:(a)@)

independence of the follow-up period in the studies
contributing in forniation;
recognition of the impact of cultural andcnvimnmental dilrcrcrlccs such as sn~oking on
normally occurring cauccr rates;

ANNEX A: EPIDEMlOMGlCAL STUDIES OF RADIATION CARCINOGENESIS(c)allowance, as necessary, for the modifying effects
on radiation risks of sex and age at exposure.

47. The f i t principle, stated in (a), concerns what iscalled risk projection Few epiden~iological studies ofradiation carcinogenesis have more than 4 - 5 0 years offollow-up information, so it is inevitable that the calculation of lifetime risks involves extrapolation beyond thetime period covered by most studies, especially for persons
exposed early in life. When presenting lifetime risks it isimportant to indicate explicitly the approach taken and theeffects of projection beyond the period covered by the dataon which the underlying risk models are based. hi several
reports, including the UNSCEAR 1988 Report [U2], theprojection effects were assessed by comparing lifctinierisks calculated for constant absolute risk niodels withthose calculated for constant relative risk models. Since
constant absolute risk models no longer appear toadequately describe the variation in risk of radiationinduced cancer with time, this comparison does notprovide useful information on the effects of risk projection.

48. The principle statcd in @) involves using descriptionsof risk estimated for one population to predict what might
be seen in a population with different site-specific cancer
rates. Extensive data on the variation in cancer rates aroundthe world have been presented by the International Agency
for Research on Cancer w17,PlO]. Sonic exaniplcs oftugh and low cancer rates in various populations are given
in Table 1, h n which it car1 be seen that site-specificcancer rates can differ by as much as two orders ofmagnitude, as do, for example, rates for nasopharyngeal
cancer, and that such great differences are not uncommon.
While some of the differcnm are due in part to reporting
methods, they also undoubtedly reflect real differences inincidence rates. Of particular interest is the contrast between
ratcs for cancers of the stoniach, lung and breast in the
population of the whole of Japan and hi the populations ofsome countries, particularly western ones. Although
Japanese stomach cancer amiual rates have bcen Llling in
rccent years, they are still much grcalcr than those inwestern Europe or the United States (50-60 per 100,000 per
year compared to 6-10 per 100,000 per year). Stomach
canccr rates in the Russian Federatiori and other parts of theformer Soviet Union average 40 per 1 0 , 0 0 0 pcr year but
arc quite variable across the country. On the other hand,
despite the fact that breast cancer rates in Japanese women(about 25 per 100,000 pcr year) arc increasing, they are stillless than half those in Europe and the United States (55-90
per 100,000 per year). Lung cancer rates also tend to belower in Japan (25 pcr 100,000 per year) than in manyother muntries (#a per 100,000 per year). The
differences reflect variation in the levels of exposures tocarcinogens other than radiation and, in some cases,
variation in the susceptibility of different ethnic group.
49. Such differencesin background rates of cancer raisequestions about the applicability of risk estimates to a21

population other than the one for which they were derived.
Modern analytical methods allow the development oftime-dependent models for excess absolute or relative risks
that provide mniparable descriptions of the current data
for a specific population, but they can lead to different
lifetime risk estiniates when applied to populations withdifferent cancer incidence. Despite the large number ofstudies of radiation and cancer in humans, it is still unclear
how best to ttansfer risk estimates to different populations.
This issue is discussed further in Chapter TI.
50. The calculation of liCetime risks requires a set of
normally occurring death rates from all causes and fromthe specific causes of uiterest for models of radiation
effects, These are usually cross-sectional rates, i.e. rates fora specific year or averages over a limited number ofconsecutive years, for a specific national or uiternational
population. Since radiation-induced cancer risks vary withage at exposure and scx, the basic calculations are carriedout for each age at exposure and sex. The resulting
estimatcs are then averaged with respect to the populationof interest, e.g. the current population of Japan. While
lifetime risk estimates provide a convenient summary ofradiation effects, it should be noted that cancer ratcs
change with time. The lifetime risks are not therefore
estimatcs of what would be expected in either the
population(s) h n l which the risk models were developed
or in the populations used to obtain the background rates
for the lifetime risk computations.
51. In the UNSCEAR 1988 Report p 2 ] the primarymeasure of lifetime dehiment was the risk that anindividual would die h m a cancer that arose owing to the
exposure in question. In this Annex the term "&k of
exposure-induced death" @EID) is used for this quantity.
For an instantaneous dosc D to the whole body or to anorgan at age e, the lifetime risk of exposure-induced dcathfrom cause c (all cancers or a single canccr) is given by

where mc(alD,e) and m,(a) are the death rates from cause
c at attained age a, with and without, respectively,
instantaneous exposure to total dose D at age e, and where
S(ap,e) is the probability that the individual survives toage a given that he or she was alive and received total
dose D at age e.
The risk or exposure-induced death is not the only
nleasurc of lifetime detriment that can be used. Indeed, adiff'erent measure, the excess lifetime risk (ELR), has been
C121.
used by the BEIR IV and BEIR V Committees [a,The excess lifetinie risk is the increase in the lifetime riskof the cancer in question experienced by an individual asa result of the specific exposure. For instantaneous
52.

22

UNSCElAK 1994 REPORT

exposure to a dose D at age e, the excess lifetime risk forcause c is given by

where S(ale) is the probability that an individual survives
to age a g ~ e nthat he or she was alive at age e and theother quantities are the same as in the definition of REID.
53. Although both the REID and the ELR arc usefulsummaries of lifetinic detrinient, they measure slightly
different quantities The risk of exposure-induced deathcan be interpreted as the risk that an individual will die
horn a cancer that has been caused by the exposure in
qucstion, while the excess lifetime risk is the difference
betwcen the proportjon of people dying of cause c in an
exposed population and the proportion dying of this cause
in an otherwise identical, but unexposed, population The
difference between the REID and the ELR concerns thecou~~tingof cascs who would have died of cause c in theabsence of exposure but who die of this cause at an earlier
date following exposure. Such cases cor~tributeto the riskof exposure-induced death but are ignored ill the cxccss
lifetinic risk [T14]. The ratio of the ELR to the REID isapproximately equal to (1 - B,), where B, is the lifetime
risk for all exposure-it~ducedcauses among unexposed
persons [V4]. This implies tl~atif one considers lifeti~iic
risk for all cancers combined, the excess lifetime risk willbe 15%20% lcss than the risk of exposure-induced death,since the lifetime risk of dying of cancer is about 15%20% in most populations.

54. The e x r w lifetin~e risk has some possibly
undesirable properties, all of which arc rclatcd to thc factthat an exposure that increases an individual's chance ofdying from one cause necrssarily decreases his or her
chance of dying horn othcr causcs. Thus the excess
lifetinle risk can be negative, even if the exposure
increases the risk of cause c, if it incrcascs the risk ofother causes even more. If an exposure increases the riskof all causes of dcath to tile sarnc extent, then tl~eexcess
lifetime risk for any cause would be zero. Individuals
would then die sooner, but the distribution of causes ofdeath would bc unchanged. On the other hand, anadvantage of the cxccss lifetinle risk over h e risk of
exlmsure-induced deatlr is that it has a morc directinterpretation; it is, strictly speaking, the increase,attribulable to the exposure, in tllc probability that apenon's eventual dcath is due to the cause c. The
undesirable propertics oS both ll~eexccss lifetime risk andthe risk of exposure-induced death are largely aconsequence of efforts to reduce a time-dependent quantity
to a single value.

55. Since neither the risk of exposure-induced death nor
the excess lifctirne risk provide direct inlbmiation on thetinies at which the cxposurc-induced events occur, it isuseful to supplement estimates of these quantities with astatistic that descriies tl~csctimes. In the UNSCEAR 1988
Report [U2]this was done using a measure called "loss oflife e x p e c t a n c y V E ) . The loss of life expectancy is thedifference between the expectation of life for an individual
exposed at age e and the expectation for an unexposed
individual. For an ir~sta~~taneous
dose D given at age c, it
is given as

The loss of life expectancy depends on the tinm at which
exposure-indud events occur in the affcctcd persons (therisk of exposure-induced death). However, if the loss oflife expectancy is divided by the risk of exposure-induced
death, the result is the years of life lost per radiationThis.
quantity is more independent ofi n d u d case 0
the risk of exposure-induced dcath and can thus be thoughtof as giving additional hlfornlatio~~
about the risk. Sinceboth the risk of expurc-induced dcath and the years lost
per radiation-induced case cor~ibineidonnation over allages at exposure and also all ages at cxprcssion, they do
not fully describe the impact of exposure on a population.
Measures that display the irnpact separately for the
diflerent age groups may also bc useful. One approach tothis would be to present the cxcv.~ lifetiimc risk as afunction of attained age (A) and age at exposure (e) by,
for example, plotting ELR(Ap,c) against A, where
ELR(Ap,e) is given by equation (7) with tl~eintegrals
evaluated between e and A.
56. Finally, it should be r~otedthat even when the ratem,(ap,e) is linear in D, as for solid tunlours in the life
span study, neither the REID nor the ELR is linear, shlce
S(ap,e) is not linear in dose, especially at high dose. As
will be illustrated in the prcsentatior~ of lifcti~ne risk
estimates later in this Annex, the non-linearity is such thatlinear extrapolation from 1 Sv to 0.2 Sv, for example,
understates the low-dose estimates of risk of exposureinduced death and excess lifetime risk for solid tumours
by 10%-20%.

57. Another issue in risk estimation is how to detemiu~e
expected mortality rates following cxposurcs to low-LET
radiation at dose rates substantially lower than those thatprevail in the majority of cpidcniiological studies on which
estimates of risk Sollotvil~gexposure can be based. Given
the paucity of epidcrniological data, Ule b a t approach atpresent is probably to c a y out the risk projection for an
exposurc of interest, ignoring the possible need for a doserate effectiveness factor, and Ulcn to multiply the resultirlg
risk by a factor based on radiobiocstiniate of lifetil~~elogical as well as epidemiological considerations (weUNSCEAR 1993 Reporl [Ul 1, Annex F, "Iaflucnct ofdose and dme rate on stochastic effects of radiationnj

ANNEX A: EPIDEMIOMGICAL STUIIIES 01' RADIATION CARCINOGENESIS

58. Epidemiological studies provide the primary data on
the association between late effeds (induced cancer) in man
and exposure to ionizing radiation In interpreting theseresults it is important to remember the limitations imposedby the observational nature of such studies. Carefulconsideration should always be given to the quality of thedata collected, to confounding factors and to other possible
sources of bias (including random error in the estimates of
exposure) that may be p e n t It is important also toappreciate the special problems that arise in studies
involving low doses (0.2 Gy or less), in which the relative
risks may not be much above unity and thus may be difiicult to quanw. Even when a study has been carefully
performed and appears satisfacto~y,it is important to obtainconfirmatory evidence h m other studies carried out indifferent circumstances before drawing firm conclusions.
59. As the questions of interest in the study of radiation
effects become more refined, it has become nccto
make detailed and at times coniplex analyses to ensure thatthe full information content of the data is revealed and toensure that misleading inferences are avoided. There is aneed for a better understanding and increased ux of modem
analytical methods in radiation studies. Such niethods allow
mearchers to obtain a dearer picture of the information
provided by their data and to reduce the overreliance on
subset analyses and inappropriate significance tests. Moreeffort is needed to develop as-simple-as-possiblemethods ofdefining and presenting useful summaries of radiation effects
for human cancer risk estimation.

23

60. In extrapolating from populations that have been
the subject of a specific study to different populations
exposed in other, and perhaps hypothetical, ways, it isessential that the assumptions made about variations in
the risks of cancer with level of exposure, age at
exposure, time since exposure and background incidence of the disease are in agreement with the variations seen in practice in human populations. Furthermore, any assumptions about projected effects at longtimes after exposure, where few data are as yet available, should be made explicit. Despite the large
number of available studies, there is currently little
useful information on the question of how to transfer
risks estimated for one population for use with anotherpopulation. Careful parallel analyses of existing data
should be undertaken.
61. The measures of lifetime detriment from radiation exposure that were used in the UNSCEAR 1988
Report [U2]; the risk of exposure-induced death(REID) and the loss of life expectancy (LLE) provide
useful summaries of radiation effects. The risk of
exposure-induced death and the years of life lost per
induced case (YLC)will be used as the primary
general descriptors in this Annex. It would bedesirable to develop other measures that provide amore complete picture of the temporal nature ofradiation-induced cancer. In addition to estimates ofmortality-based risk, estimates of incidence-based
lifetime risk are also needed, and these can beevaluated with data now becoming available.

n. CARCINOGENICEFFECTS OF EXTERNALLOW-LET RADIATION EXPOSURES
62. Epidemiological studies of populations exposed
wholly or predominantly to low-LET radiation are ofprime importance in evaluating risk in enviromnental andoccupational settings. Effects have been den~onstrated
mainly in studies that involve exposures of relatively highy ,information isdose (about 1 Gy). I n ~ s ~however,accumulating on effects from lower doses (0.2-1 Gy) and,in a few instances. from doses less than 0.2 Gy.
63. Many of the studies have been characterized not
only by hlgh doses but also by high dose rates (>0.1 mGy
min-l). These include the studies of survivors of theatomic bombings in Japan (0.01 Gy i1to several gray persecond), patients treated with radiation and individuals
who have had diagnostic or prenatal x-ray examinations.
In recent years studies have also been undertaken
involving exposures at low dose rate or exposures received
as many fractions, each of low dose. These include studies

of workers in the nuclear industry and individuals exposed
to gamma rays from terrestrial mdiation or fallout from
nuclear explosions. However, it is noted in the UNSCEAR
1993 Reporl [Ul], Annex F, "Influence of dose and dose
rate on stochastic effects of radiation", that at low doses(0.2 Gy or less) the fomi of the dose response is expected
to be the same (i.e. linear) whatever the dose rate. Thus.
in some studies nominally at high dose rate the total dose
received is so low that the studies should probably beclassified along with low-dose, lowdose-rate studies.
When the dose is an absorbed dose of low-LET
radiation (e.g. from x rays) it is specified in gray (Gy).
When the dose refers to the life span study of survivors of
the atomic bombings, the dose will usually be a welghtcd
dose and will be specified in sievert (Sv), in which theabsorkd dose from neutrons is multiplied by an RBE of
10 and added to the absorbed dose from gamma rays.
64.

Furthermore, all low-LET radiations such as x rays,
gamma rays and beta particles will be treated alike, i.e.
they will be assumed throughout this Annex to have thesame biological effectiveness, even though at very low
doses well-known differences in effect occur [S67].
65. The epidemiological studies used to derive estimatesof risk of cancer following low-LET radiation exposures
are reviewed in this Chapter. The main features of thesestudies are given in Table 2 The nature of the exposuresand the dosimetry are described, as are the age, sex distribution and follow-up of the population. Also indicated in
the Table are the cancers that have been studied and thosefor which statistically significant excess risks have beenreported. Although the studies have a wide variety ofcharacteristics, an attempt is made to calculate summary
risk estimates for selected sites. However, in view of theuncertainties in specific studies and the different natures ofthe populations considered, thcse estimates should becompared and generalized with caution There is also
some discussion of the specific effects, temporal trends
and applicability of the results.

6. The diverse studies listed in Table 2 have different
strengths and weaknesses, and some are more important
than others in contributing to quantitative estimates of risk
To provide a perspective on these relative merits, some ofthe strengths and weaknesses are outlined in Table 3. The
attributes considered include the composition of the population studied, the nature of the control group, the lengthof follow-up, the ascertainment of incidence or mortality,
the range of doses to those exposed. the nature and qualityof the dosimetry and any unusual or specific uncertainties.
It is not possible to be completely uniform or comparable
in making these assessments. The comments in Table 3
are somewhat subjective and are provided principally as
general guidance.
67. All the studies to be considered by the Committeethat are relevant to risk estimation for low-LET radiation,
including external and internal radiation at high and low
dose rates and dose, are included in Table 2. The numerous other studies in the literature, some of which haveraised interesting points from time to time, but others ofwhich have hiled to make useful contniutions to theestimates of risk, are not considered further here.

68. Risk cstimatcs based on the continuing follow-up of
the life span study of su~vivorsof the atomic bombings inJapan have been the primary source of information on therisk of hlghdose-rate exposures to mainly low-LET
radiation. However, there are now a large number of otherepidemiological studies that can make important contnbutions to the understanding of cancer risks following highdose-rate exposures to low-LET radiation.

69. The life span study has a number of features thathave allowed it to play a central role in the estimation ofradiation risks, notably the large number of exposed
persons of both sexes and a broad range of ages, thewhole-body exposures of individuals in the cohort, theinclusion of a large group of people who received very
low doses, which can be used as an internal control group;
the completeness of the mortality follow-up; and theavailability of data on cancer incidence.
70. Despite the strength of the life span study, anumber of factors make it essential to consider otherexposed populations. For example, the exposure was
highly acute (a few seconds at most), and since the life
span study is composed exclusively of Japanese, risk
estin~atesderived from this cohort cannot directly provide
infonnation on the application of the risk estimates toother populations. This latter point is especially importantbecause of differences between site-specific canccr incidence arid death rates UI Japan and in other countries.
General cancer patterns in Japan have some notablefeatures relative to patterns in European or h e r i m
populations, including the high incidence of stomach
cancer, the low rates of female breast cancer and thevirtual absence of chronic lymphocytic leukaemia. Risk
estimates from other studies can provide important additional infonnation about risks for specitic cancers or, insome cases, more general aspects of the risk of radiationinduced cancer, includulg factors such as age at exposure.
sex, temporal patterns of the excess risk and the effects offractionation.

71. The studies most useful for comparison with and asa supplement to the life span study involve populations
exposed to x rays for diagnostic or therapeutic purposes.
The features of the exposures and populations of the mainstudies are summarized in Table 2, as already noted. Asa group, studies of medically exposed persons have anumber of specific lin~itationsnot noted under strengths
and weaknesses given UI Table 3, including the following:(a) the disease under treabnent or observation may
affect subsequent cancer risks:patients
may have been exposed to other carcine@)
gens as part of their medical treatment, e.g.
alkylating agents in cancer therapy;
therange of ages at exposure is often n a m w and(c)the data are often limited to, or include a very highproportion of, a single sex;(d) the doses are in a limited range, the exposures areusually tageted to a specific tissue and the dose
estimates to specific organs are sometimes not ofgood quality.
72. Another important group of studies relevant to theassessment of cancer risks following high-dose-rate,
low-LET radiation exposures involves the hlghly
fractionated exposures received by radiologists and othermedical x-ray workers [A9, E7, M24, S38,W10,W14j.

ANNEX A: EPIDEMIOLOGICAL STUI3IES OF RADIATION CARCINOGENESIS

Dose estimates in earlier studies were often laclung, while
in some more recent studies doses are assigned on thebasis of year of exposure and knowledge of radiologicalprotection practices in the relevant country at that time.
Such studies cannot therefore be expected to provide
precise information about risk estimates.

73. Despite the limitations of any slllgle epidemiologicalstudy of radiation risk, studies of populations withappreciable exposures to low-LET radiation are importantto an understanding of radiation risks because they offer
information on risk in a number of ethnic groups andnationalities and because the conditions under which theexposures were received vary so greatly [D27].
1. Mortality and incidence in the life span study
74. The cohort of the life span study includes 93,000
survivors of the atomic bombings and 27,000 persons who
lived at Hiroshima and Nagasaki in 1950 but who were
not in the cities at the time of the bombings. The primaryfindings of the life span study have been used to clarify
the association between radiation exposun: and cancer
mortality. The life span study cancer mortality data for theperiod 1950-1985 [S7, S69] were used as the basis of risk
estimates for the UNSCEAR 1988 Report [U2]. In thefollowing text, mortality data extended to 1987 or specified for the period 1958-1987 are described in order tocompare with incidence data for 1958-1987 [Ru, T15j.

75.

A complicating factor for estimates of low-LET
cancer risks based on the life span study arises from thepresence of a small, but not negligible, neutron component, especially at Hiroshima, where neutrons accounted
for 1Ye2% of the organ doses, with individual neutron
dose estimates ranging from 0 to 100 mGy. The high correlation between a survivor's estimated gamma andneutron doses makes it impossible to use the life spanstudy data to provide reliable estinlates of the neutron
relative biological effectiveness (RBE). Therefore, it has
been common practice to assume a specific value orvalues for the RBE of neutrons in the computation of life
span study risk estimates. Published analyses of the life
span study data have usually made use of tom1 absorbed
dose, i.e. they have implicitly assumed an RBE of 1, or
they have explicitly assumed a constant RBE of 10 or 20.
While it has been demonstrated that risk estimates basedon the DS86 dosimetry do not vary greatly with theassumed value of the RBE in this range [P3, S6], preference should be given to estimates based on values of
10-20. Questions raised recently about the magnitude of
the neutron component [ S 6 ] are discussed in paragraphs
156158.
76. Although important questions about the dosimetry of
the swivors of the atomic bombings remain [ S 6 ] , theavailability of detailed data on location and shielding at the25time of the bombings makes it possible to compute individual dose estimates. Uncertainties in the location andshielding data are a major component of the random uncertainty in the individual dose estimates. In recent ycanmuch attention has been paid to characterizing the natureof random errors in life span study dose estimates and toassessing their impact on risk estimates [P9, P31, R22, S55J.

77. Recent reports of the life span study provide data on
cancer incidence in the period 19581987 for solid
tumours [TI51 and in the period 1950-1987 for leukaemia,
lymphoma and multiple myeloma p33]. The life spanstudy incidence data allow a more precise description ofradiation-induced cancer risks both because of the larger
number of cases in the incidence data than in the mortality
data and because the registry-based diagnoses are of better
quality than cause-of-death data from death certificates.
The primary limitations of the incidence data are the lackof data on solid tumour incidence for the Grst seven years
of follow-up (data on the Grst five years after exposure areunavailable for study for either mortality or incidence inthe life span study) arid the problems that arise owing tomigration from the tumour registry catchment areas. Life
span study migration probabilities depend on birth cohort,city and age. Among life span study members under theage of 16 years in 1945, roughly 25% of those from
Nagasaki and 15% from Hiroshima were not resident inthose cities in recent years. Older survivors were muchless likely to have moved, and it appears that those whohave left the area tend to return when they reachretirement age. In both cities, men were more likely to
migrate than women. Migation probabilities were taken
into account in the recent analyses of the life span study
cancer incidence data [S23, T151. The incidence andmortality data for solid turnours in the life span study are
given in Table 4. While the life span study incidence data
are important, they should be viewed as a supplement to.
rather than as a replacement for, mortality-based risk
estimates in the life span study. In particular, it is likelythat both mortality- and incidence-based risk estimates will
be hiportant in the quantitative evaluation of radiation
effects in human beings.
78. Estimates of the average excess relative and absoluterisks for solid turnour incidence and mortality in the life
span study are compared in Table 5 and illustrated in
F i r e I. The organ-dose-based cancer mortality risks
derived by Shimizu et al. [S7, S69] for 1950-1985 were
calculated assuming an RBE of 1. When organ-dose-basedrisk estimates were not available, approximate estimates
were made by dividing the shielded-kerma-based values
by estimates of the transmission factor for the target organ.
The values for cancer mortality [R23] and cancer incidence [TlS] for 19581987 are based on weighted organ
doses (with the absortxd dose from neutrons given aweight of 10, i.e. a constant neutron RBE of lo), which
are similar to equivalent doses and will be given in sieven
The 95% confidence bounds in the original papers wereNISNEX A: EPIDEMIOLOGICAL STUD1IES OF RADIATION CARCINOGEWSIS

expected numbers of solid tumours were derived fiom
models similar to those described in PlS] and [R23]. Life
span study mortality risk estimates are based on the 19501987 data presented in [R23]. Life span study solid
tumour incidence risk estimates are derived from the
1958-1987 data used in p15]. For the life span study
lympho-haematopoietic cancer data, the time-dependent
excess absolute risk (EAR) models for 195CL1987
presented in p33] were used. For other cohort studies, theexpected numbers were determined iiom publishedreports. If the study included a control group and if
information about observed and expected numbers of casesin this group was available, a correction was made to the
expected number:where EE and E: are, respectively, the adjusted andunadjusted estimates of the expected number of cases inthe exposed portion of the cohort and OOand Eg are theobserved and expected number of cases in the unexpcsed
portion of the cohort If the cohort included no internal
controls, no adjustment was made. The estimates of theexcess relative risk and the average excess absolute risk
were calculated directly from these values. The linear
excess relative risk coefticient iswhere 0, is the observed number of cases and 6 is theaverage dose in the exposed portion of the cohort The
linear excess absolute risk coefficient per person-year ofobservation isDifferences in time-averaged absolute risk coefficients fordifferent age-at+xposure groups must be interpreted withcaution, since current data suggest that excess absolute risk
coefficients change with increasing time after exposureand follow-up is inconiplcte for the younger members ofmost cohorts used in the studies of radiation effects (seeSection lI.A4).
85. Confidence intervals for studies other than the life
span study were obtained using exact Poisson methods andassuming a linear dose response. These methods tend tounderstate the uncertainty in the estimates, especially when
the average dose is much greater than 1 Sv or when theinternal control group is small or non-existent For the life
span study, confidence intervals were taken from therelevant publications. This was done because confidence

27intervals for risks calculated from the data of the life spanstudy given in Table 8 are too wide, since information on
the low-dose group used in the computation of the
expected number of cases is not included in this Table.

86. For case-control studies, risk estimates andconfidence intervals were taken
the original papers
whenever possible. In some cases, odds ratios were
calculated based on unmatched analyses of published data.
Excess absolute risk estimates are given for case-control
studies in which the cases were obtained by complete
ascertainment in a well-defined cohort and sufficient
information was given to allow calculating the number ofcases expected in the full cohort under the null hypothesisof no radiation effect
87. The risk estimates lor selected cancers are given inParts I-XIV of Table 8. Listed in order of the international
statistical classification of diseases, injuries and causes ofdeath GCD) code, each part is dedicated to one type orsite of caner. Figure II, which, in analogy with Tablc 8,
also contain.. Parts I-XIV, illustrates the excess relative
risks per sievert Although both the Table and the Figure
facilitate the comparisons of risk estimates, it must be
repeated that the validity of the comparisorls is impededby the various exposure conditions, daimetric evaluations
and population-related factors. It is also important not tooveremphasize the significance of differences in the risk
estimates for specific cancers. While there are probably
real differences in the magnitude of radiation effects for
specific cancers, there is also a tendency to overinterpretthe observed differences. Recent joint analyses of cancerspecific excess risks derived from the life span study
mortality data [Pu)] suggest that differences in tbe excess
relative risks for specific cancers are generally about what
can be expected on the basis of random variation about acommon level of risk for these s w i c cancers. The
expected numbers of cases for the life span study were
calculated using slightly different methods than were usedin other estimations of the typical average relative risks (asgiven, for example, in Table 5). In some cases, this leads
to slight differences between the estimates in Tables 5 and8. These differences largely reflect the variability inherent
in these data.
(a)Cancer of the oesophagus

88. Risk estimates for oesophageal cancer are presented
in Part I of Table 8, and the excess relative risks areillustrated in Part I of Figure 11. Data on the incidence ofoesophageal cancer are available fiom the life span study[TI51 and the cervical cancer cohort study [Bl 1). The risk
estimates are similar in the two studies, but in neither caseare they statistically significant Data on mortality fromoesophageal cancer are available fiom three studies. A
statistically significan~ association between radiation
exposure and cancer of the oesophagus is reported only inthe ankylosing spondylitis study [D6, L6]. In an earlier

UNSCEAR 1994 REPORT

28

analysis of the life span study mortality data [S7], asignificant excess risk of oesophageal cancer had been
noted. Davis et al. [Dl41 noted a sgdicantly elevatedstandardized mortality ratio for oesophageal cancer in thecohort of the Massachusetts tuberculosis fluoroscopy study[D14], but large oesophageal cancer standardized mortality
ratios were also seen anlong unexposed members of thiscohort Once this is allowed for, there is no evidence of aradiation effect or a dose response. The authors speculated
that the large standardized mortality ratios for both
exposed and unexposed members of this cohort wereassociated with alcohol and tobacco consumption.
89. Variations in the risk of oesophageal cancer with age
and sex. as seen in the life span study, are generally
consistent with the pattern seen for many other cancers,
i.e. a larger exccss relative risk for females than males andhigher average relative risks in those exposed before theage of 20 years. None of these differences, however, isstatistically significant In spite of some conflicting
evidence, the mortality data of the life span study for
1950-1985 showed a significant risk for oesophageal
cancer mainly because of its occurrence in the period 5-12
years after exposure. Thus the oesophagus may be remgnbed as having a positive risk for relatively early occurring
radiation-induced cancer, but when the dose is fractionated(as in the Massachusetts tuberculosis fluoroscopy study)
the risk is very small.
(b)

Cancvr of the stun~ach

90. Part II of Table 8 and of Figure TI compares risk
estimates for stomach cancer. A statistically significant
associationbetween radiation exposure and stonlach cancer
is shown in the incidence data of the life span study [TI51
and cervical cancer case-control study [B21] and in themortality data of the life span study [R23] and the peptic
ulcer study [Gll]. Despite the very large mean dose in the
peptic ulcer study, the point estimates of the excess relative risk based on these data are only slightly less thanthose in the other populations. A non-sig~uficantestimateof risk of stomach cancer was observed 5-24 years after
exposure in the mortality data of the ankylosing spondylitis study [D6, L6].Although non-significant, the largest
point estimates of risk were obtained from the mortality
data of the metropathia haemorrhagica study [DB].
The
relative risk of mortality h m stomach cancer based ondata of the benign gynaecological disease study [I81 issimilar to that of the life span study but not significant
91. Differences in the excess relative risk of stomach
cancer with sex and age at e x p u r e are statisticallysignificant in the life span study data. &her values areshown for lemales than for males (incidence andmortality) and for those Icss than 20 years old at exposure(incidence only). Differences in the exabsolute risks
for males and females are more pronounced in the incidence data than in the mortality data of the life span study.

Current results suggest that there is an association between
low-LET radiation exposure and stomach cancer risk, withfemales having greater relative risks and perhaps also
greater absolute risks than males.
(c)Cancer of the colon

92. Risk estimates for cancer of the colon are given inPart ID of Table 8 and of Figure II. There is a clear
association with radiation exposure in both the incidence
and mortality data of the life span study p,
TI51 andin the mortality data of the benign gynaecological disease
study IT81 and tile metmpatl~iahaenlorrhagica study [D23].
The excess absolute risk estimate derived fiom data of thebenign gynaecological disease study p8] is much higher
than that derived from the life span study, reflecting thedifference in nonnally occuning rates of colon cancer in
the United States and in Japan. Two other studies provide
data on cancer of the colon. These arc the cervical cancer
case-control study p 2 1 ] and the peptic ulcer study [Gl 11.
Both involve either very high doses or a broad range ofdoses, and in both cases the estimated risks are low.
93. The sex-specific risk estimates for cancer of thecolon Gom data of the life span study differ from those forcancer of the stotnach, in that both the excess relative risk
and the excess absolute risk are higher for males than forfemales. However, the difference in the excess relative
risks is not statistically significant. (No formal test of sexrelated differences in the excess absolute risk has k e nreported.) Although the difference in the excess relative
risks for colon cancer with age at exposure is not statistically significant in the incidence data of the life span study[T15], statistically significant decreases in the excess
relative risks with tune have been reportd for both theincidence and mortality data [R23, S7]. Taken together,
the results of the studies considered here indicate an increased risk of colon cancer following radiation exposure.

(d)Cancer of the liver

94. Altl~oughan association between thorotrast exposureand liver cancer has been demonstrated in several studies(see Section IU.B),the evidence for excess liver cancer
following exposure to low-LET radiation is weaker. The
risk estimates derived from several studies are given inPart IV of Table 8 and of Figure II. With the exception of
the life span study, the numbers of observed cases are
small in these studies. None of the medi~lllyexposed
populations considered here suggests an association
between radiation exposure and liver cancer. Evidence foran excess risk of liver cancer in the life span study has
increased with additional follow-up time and the availability of cancer incidence data [TlS].
95. Interpretation of the data on liver cancer in the life
span study has been hampered by questions about theadequacy of the diagnoses. Because death ~ e ~ c a t e

A N N M A: EPIDEMIOLOGICN, STUDIES OF RADIATION CARCINOGENESIS

diagnoses of liver cancer in the life span study do not
usually allow for a distinction between primary andsecondary turnours, analyses of the life span study
mortality data [R23, S7] were limited to those cases inwhich the death cedficate explicitly identified the cancer
as primary. As indicated in Table 8, this greatly reduces
the number of cases and, in contrast to an analysis that
includes liver cancer deaths specified as primary or not
specified as secondary or primary, no statisticallysignificant radiation effect is found. A supplementary
analysis of the incidence data of the life span study [TI51
restricted to the 40% of tumour registry cases withhistologically confirmed diagnoses resulted in an excess
relative risk that was stalistically significant, with the pomt
estimate almost identical to that seen in the analysis of allliver cancer cases.

96. In contrast to most other cancets, the excess relativerisk of liver cancer for females was less than that formales. Neither the sex nor age-at-exposure differences
scen in the life span study were statistically significant
However, if females actually have lower excess relative
risks than males, then the failure to see any evidence of
exccss risks in cohorts of the benign gynaecologicaldisease study [I81 and in the cervical cancer cohort study[Bl 11 is perhaps not surprising.

97. The life span study data. particularly those on cancer
incidence, support the conclusion that liver cancers are
induced by radiation exposure. Interpretation of mortality
data of the life span study is complicated by the use ofdifferent criteria for case definitions: nonetheless thenlortality results appear to be cot~sisteatwith the incidence
results. Studies other than the life span study provide little
evidence for or against cancer risks owing to the small
number of cases.
(e)Cancer of the lung

98. The life span study [R23, T151, the ankylosing
spondylitis study @Xi,L6] and the peptic ulcer study[ G l l ] all indicate an association between radiation
exposure and lung cancer (Part V of Table 8 and of
Figure II). The lower excess relative risks in the last two
studies do not seem particularly surprising because both ofthese cohorts have a relatively high proportion of males,
and the life span study results indicate that exccss relative
risks are much higher for females than for males. The
difference in sex-specific e x m relative risk for lungcancer in the life span study almost certainly reflects
differences in rates of lung cancer occurring normally;
however, the differences in the sex-specific average ex=
absolute risks also appear to be large. Since the number ofcases is relatively large, the failure to see a significant
excess risk of lung cancer in the Massachusetls tuberculosis fluoroscopy study [Dl41 is surprising in view of thehigh excess relative risks for females in the life span

29

study. In the Massachusetts tuberculosis fluoroscopy study,
fractionation may have had a large effect It is noteworthy
that standardb. mortality ratios for both the exposed andunexposed members of the tuberculosis col~ortare verylarge. Recently published analyses of lung cancer data for
the Canadian fluoroscopy cohort [H43] support theMassachusetts findings of no excess lung cancer risk forhighly fractionated x-ray exposures. However. it should
also be noted that an excess relative risk of 0.08 G ~ ' ' wasfound following radiotl~erapyto the breast, which involved
average exposures to the lungs of about 9.8 Gy FXl, N8].
This positive but lower than expected risk may have been
reduced because of cell-killing effects after high doses.

99. It has been suggested that the relative risk of lungcancer decreases with time since exposure, as indicated in
the risk model used by the BEIR V Committee [C12].
The life span study incidence data F 1 5 ] indicate that theexcess relative risk has decreased only slightly with thepassage of time and that the excess absolute risk is
continuing to increase. This contrasts with the finding of
no apparent excess during the period beyond 25 years
after exposure i n the ankylosing spondylitis study. It is
important in any study of respiratory cancer to indicate thesmokmg status of the population, as the joint effeds ofsmoking and radiation alter the dose response (seeparagraph 182).
100. In summary, an elevated risk of lung cancer is seen
following acute exposure to low-LET radiation. The
fluoroscopy data suggest that highly fractionated exposures
may have little or no effect Although descriptive models
that allow for decreases in lung cancer risk with time since
exposure have been proposed, current low-LET data do
not appear to provide strong support for this notion
Therefore, lung cancer risk estimates presented later in thisAnnex are based on time-constant relative risk models
with sex and age-at-exposure effects.

(0

Cancvtr of the bone and connective tissue101. Although cancers of the bone and connective tissue
are relatively rare, a number of studies have noted excess
risks for thcse cancers following radiation exposure (PartV1 of Table 8 and of Figure U). However, only for theskin haemangioma in childhood study IF121 and thechildhood radiotherapy study [T6] are the results
statistically significant. In the latter study, a dose response
was evident over intervals of therapeutic doses. A study ofalso found a very
children irradiated for reti~~oblastoma
high risk of osteosarcoma and soft tissue sarcoma
associated with radiotherapy exposures PI. A large,
statistically siglificant excess risk for cancer o i the bone
and c o ~ e c t i v ctissue was also reported for the children in
the tinea capitis study in Israel [NO]. However. since theskeletal dose was not reported, it is not possible to present
estimates of the risk per unit dose. Although the numbers

are small, the age- and sex-specific estimates based ondata of the life span study and other populations suggestthat survivors expcMed before the age of 20 years may
have high relative risks.
(s)Non-melanonia skin cancer

102 As can be seen in Part W of Table 8 and of Fire11, elevated risks of skin cancer have been reported m anumber of studies. The most detailed analyses of data on
low-LET radiation and skin cancer come from the tinea
capitis study in Ncw York [Al, SS],from the tinea capitis
study in Israel p10,R191 and from the life span study on
cancer incidence [TlS]. Sig~lificantassociations between
radiation exposure and lion-melanoma skin cancer
incidence have been shown in these studies and in theRodrester thymic enlargement study, the lymphoidinadiation study and the thyroid irradiation study, allevaluated in the review by Shore [S62].Non-significant
risk estimates arc derived from data of three other studies
included in Part VII of Table 8.Those exposed at younger
ages have been found to have significantly higher relative
risks in both the life span study and the Israeli tinca capitis
study. The issue of age was not investigated in the New
York tinea capitis study. The New York studies suggestthat persons with lighter skin am at higher risk ofradiation-induced skin cancer, especially in areas of skin
exposed to sunlight, c.g. the face. None of these studies
indicates that the excess relative risk depends OII sex. The
life span study results sugcst that the dose response is
non-linear with little or no effect at doses below 1 Sv.
103. The similarity of excess relative risks for skin cancer
evaluated from the main studies in Part VII of Table 8
should not be ovcrintcrpreted, s i n e the life span study
includes older survivors who have lower risks while thetinea capitis studies include different proportio~lsof lightand dark-skinned patients. For the younger persons in thelife span study, the cxccss relative risk appeared to begreater than that in the Israeli tinea capitis study. In Japan,
the incidence of skin callcer in normal circumstances isquite low. In the cervical cancer cohort study, only 206
non-melanoma skin cancers were observed, with 220
expected. The absence of a risk following high-dose
exposures to Lhe skin of these patients is noteworthy.
Comparison of absolute risk estimates for skin cancer isproblematical because of differences in the exposed areaof skin in the various studies. Excess risk to medically
irradiated patients occurred only to areas of skin also
exposed to ultraviolet radiation [S62].

(h)

Cancer of the female breast

105. Elevated risk of breast cancer follawing exposure
has been den~onstratcdin several studies, including tbe life
span study [T2, T15], the Massachusetts tuberculosis
fluoroscopy study @331],tuberculosis fluoroscopy studies
in Nova Scotia and other Canadian provinces MI91 andthe acute post-partum mastitis study New Y& [S9], as
can be seen in Part VIU of Table 8 and of Figure Il. Wideconfidence intervals are indicated for the d i o s i s patients
study [H24], the Rochester thymic irradiation study p 2 ]and for women in the ankylosing spondylitis study [D6,L6]. A number of studies have considered radiation
exposure and breast cancer but provide little or noconvincing evidence of an association: the contralateralbreast studies in Denmark [S60]and in the United States
18181;the cervical cancer case-control study [Bll,B20,
B21];the Israeli tinea capitis study w20];and for womenin the Swedish skin haernangioma study F12].
106. The failure to detect en increased breast cancer riskin the cervical cancer case-control study is somewhat
surprising in view of the large number of cases andmoderate doses (average 0.3 Gy). However, as suggestedby the very different estimates of excess relative risk forthe younger and older populations (see Part VIII of Table8),breast cancer risks following radiation exposure exhibita reasonably consistent decrease with increasing age at
exposure (see paragraph 137). Thus, the hilure to detect
radiation ell'ecb in the cervical cancer case-control study
and in the contralateral breast studies [B18]is possibly due
to the fact that these cohorts include a large number ofwomen who were over 35 years of age at exposure.
Indeed, a significant excess risk of breast cancer was
fou~ld in a subset analysis of younger women in the
con~rala~cnl
breast study in the United States p18]. I1 has
also bee11 suggested that the lack of an increased risk ofbreast cancer in the cervical cancer case-control study isrelated to the cessation of ovarian function caused byinadiation [B20].However, when the data on cervicalcancer were restricted to cases anlong women whare
ovaries had been removed before or shortly after the
diagnosis of cervical cancer, a positive, though 1101
statistically significant, effect was seen. The Hodgkin's
disease patient., study clearly indicates a radiation effectwith the highest risk at young ages [H2, T81. Also, therisk per unit dose appears to be lower after high d mthan is sugcsted in studies at low doses, which could be
due to cell-killing, liniiting the number of cells at risk (=pardb~aph171).

107. Relative risks appear to be especially high anlory
104. Present results sugcst that elevated skin cancer risks
are associated with low-LET radiation exposures. Relative
risks for children are grcater than those for adults.
Questions about the shape of the dose-response function
and of a possible interaction between high- and low-LFT
radiation exposure warrant further examina t'1011.

W ~ I I I C I Iwho were exposed to radiation as children, as

indicated by the results of the life span study, theRochester thymic irradiation study and the scoliosis study.
The risk estinlates for the cohort of scoliosis patients are
based on only 11 cases, with 6 expected, and are probably
biascd upward as a consequence of factors unrelated toANNEX A: EPIDEMIOLOGICAL STUIIIES OF RADIATION CARCINOGENESIS

exposure, such as a bycater rate of nulliparity among
women with severe spinal curvature. A relatively large
effect (an excess relative risk of 1.11) at very low doses(16 mGy) has been reported in the Israeli tinea capitis
study WO]. This finding should be viewed with some
scepticism, since it is based upon results for a specificsubgroup. which had an unusually low number of cases in
the control poup. Compared with general population rates
there was no excess.
108. In general, constant relative risk models that have alinear dose response and that depend on age at exposure
appear to describe the breast cancer data quite well withincohorts. Based on a parallel analysis of the incidence datafrom the life span study and two cohorts from the UnitedStates (the Massachusetts tuberculosis fluoroscopy studyp31] and the New York acute post-partum mastitis study[S9l), it was concluded that although relative risk models
describe the data well within a single population, average
excess absolute risks appear to be similar a a w
populations [U].
In the analysis canied out by the BEIR
V Committee [C12], it was suggested that a common
relative risk model for the three cohorts fit the data better
than did a common, time-dependent absolute risk model.
In the same report, a similar conclusion was reached basedon a comparison of breast cancer mortality in the life spanstudy and the Canadian tuberculosis fluoroscopy study
w 1 9 ] . These results suggest that fractionation has little
effect on breast cancer risk. This is in marked contrast to
the results for lung cancer in the tuberculosis cohorts
fD14, H43], in which no increased risk was seen.
Although the simple summary statistics shown in Table 8
cannot be used for detailed formal comparisons, becauseof differences between cohorts in age at exposure andother factors that might affect the risk, the results of thestudies suggest there is a need to carefully consider themast appropriate risk niodel for transfer between populations. Breast cancer risks are clearly elevated following
low-LET radiation exposures Relative risks are higher for
women early in life, including wonien expased prior tomenarche.

6)

h e r of the urinary bladder

109. Estimates of risk for bladder cancer fioni several
studies are given in Part D( of Table 8 and of Figure II.
Statistically simcant excess risks have been derived forincidence data [TI51 and for mortality data [R23] of thelife span study, the metropathia haeniorrhagica study
ID231 and the bcnign gynaecological disease study P8J.
Although the doses are considerably higher in the last two
studies and in the cenjical cancer case-control study [B21],
the risk estimates are about the same as the non-significant
risk estimate in the ankylosing spondylitis study PI.
Within the life span study the effects of age arid sex on
the risks are unclear. In particular, the incidence data
exhibit a statistically significant sex difference, with theexcess relative risk for females exceeding that for males31

by a hctor of about fwe but the average excess absoluterisk showing no significant difference; in the mortality
data, the point estimate of the excess relative risk formales is higher than that for females, although thedifference is not statistically signifiolnt Neither the
mortality data [S7] nor the incidence data [TI51 in the life
span study exhibit statistically s~gniticantvariation withage at exposure for either the excess relative or absoluterisks; however, there is a suggestion of some variation
with age in the cervical cancer case-control study p21].
110. In summary, statistically significant excess risks ofcancer of the urinary bladder are seen in several
populations exposed to low-LET radiation. The life spanstudy risk estimates are somewhat greater than those inother studies, however, since those other studies involve
much higher doses, the differences may reflect cell-killing.
(j)

Turnours of the brain and central nervous system

111. Risk estimates for tumours of the brain and central
nervous system are presented in Part X of Table 8 and of
Figure U Fairly large and statistically significant excess
relative risks have been demonstrated in both tuiea capitis
studies [Al, RlO] and in the ankylosing spondylitis study[D6, L6]. A lower, but still siwficant, risk is estimatedfrom the data of the pituitary adenoma study in the United
Kingdom [Bg]. Slgruficant risks were not seen in either thelife span study or in the skin haemangioma study [F12j.
Except for the ankylosing spondylitis study and the pituitary adenonia study, the studies showing significant risks
involved children. It has been noted that some of the cases
in which brain tumours were recorded on death certificatesin the ankylosing spondylitis study may have involved
secondary tumours from lung cancer [El. The tiriea
capitis study in Israel included both benign and malignant
tunlours of the brain, with 42 of 60 tumours king benign(niostly nerve sheath tumours). The life span study also
included both bcnign and malignant brain tumours.
The mortality data [R23] and incidence data
[TlS] of the life span study provide weak evidence of an
association between radiation exposure and cancers of thecentral nervous systcni excluding the brain. The estiniatcs
from the incidence data [TI51 suggest the possibility of
diKerences rclatcd to sex and age at exposure, but thesedifferences are not statistically significant A number ofother studies have reported significant increases in brain
tuniours and tumours of the central nervous systemassociated with various types of radiation exposure.
including prcnatally exposed individuals p23, h49],
persons receiving radiation therapy for childhood cancers[A2, R14], persons treated for enlarged tonsils [S32] andindividuals who received radium implanb in thenasopharynx [S3]. Preston-Martin et al. have rcported an
association between dental x rays and brain tuniours [PS,P6, P14] and between malignant brain tumours and otherfactors in a study in the h Angeles area IP21, P22j.
112.

1991 REPORT113.
The results of these studies suggest that low-IJT
radiation may be associated with increased risks oftumours of the brain and the central nervous system andthat risks for those cxposed as children may be greaterthan for those exposed later in life.
Q

Cancvr of the thymid

114.
Risk estimates for thyroid cancer are presented inPart XI of Table 8 and of Figure IT. The compilation isbased on a review by Shore [S61]. Excess risks have beenfound in a large number of populations. B e c a w of thestrong association between age at exposure and the excess
relative risk for thyroid cancer seen in most studies, results
for childhood and adult exposures are separated in boththe Table and the F i r e . Since the detection of thyroid
cancer is heavily dependent on the degree of screening.
average excess absolute risk estiniatcs are not comparable
even for studies that have equal follow-up intervals andsimilar age and sex distributions. This is illustrated by the
results for the Michael Rcese tonsil study [S63]. An
extensive thyroid cancer screening progamnie was started
in this cohort in 1974, after which thyroid cancer rates in
the cohort increased alriiost 10-fold. The impact of thisscreening programme is apparent in Table 8. While theexcess relative risk cstin~atc for this study is roughly
comparable to that seen in othcr populations, the absoluterisk cstimi~tc is much larger than that in any otherpopulation co~aidcred.Schncider et al. [S63] estimated thescreenin adjustcd cxcess absolute risk to be 1.7 10"(PYSv) (weightcd dose, RBE = 1 for x rays).

-f-

115.
Excess relative risks for incidence of thyroid
cancer in children based on data of the life span study[TI51 were 10.3 for thosc of age 0-9 years and 45 for age
10-19 years. Values From other studies are comparable,with the exception of the tuberculosis adenitis screening
study [Hl] and the Israeli tinea capitis study [R15]. Thevery large risk estimate and narrow confidence interval forchildren in the tuberculosis adenitis screening study [HI]is a consequence of the small expected number of cases.
Case ascertai~wientwas very good in the Israeli tinea
capitis study (RlS], and unlike rliany of the other thyoid
cancer studies, there is an intcrnal control p u p . Risk
estimates in this study appear to be quite large a n 4 as
noted in paragraph 169, fflcre are some uncertainties
regarding thyroid doses in this cohon Shore et al. [S54]found significantly greater excess relative risks for Jewish
than for non-Jewish children in their study of thymic
irrddiation in infancy.
Age-atcxpmurc effects are apparent in all studies
116.
in which this factor can bc evaluated, such as h e h c acapitis studies, the life spa11study and even some studies
that involve only a liniitcd age range. Sex-specific excess
relative risk estimates for thyroid cancer are similar,
despite the fact that the riitc of naturally occurring thyroid

cancer in fernales is typically three times the rate in males.
This can be seen fro~nage- and sex-specific estimates in
the life span study, but is equally apparent from the Israeli
tinca capitis study [R15) and othcr studies. While neither
the life span study nor the Israeli tinca capitis study shows
any statistically signific-ant variation in age-at-exposure
specific relative risks aver time, data from the somewhat
smaller Rochester thymic irradiation study suggest that therelative risk decreases with time.
117.
In summary, low-LET radiation exposures,
possibly at doses as low as 0.1 Gy, are associated withsignificant excess risks of thyroid cancer in children The
excess risk for adults appears to be laver. In contrast to
the pattcrn seen for many othcr solid tumours, excess
relative risks are similar for males and females despitelarge differences in the sex-specific background rates inmost populations.

118.
Risk estimates for lcukaemia are presented inPart XII of Table 8 and of Figure II. Estimates can bemade from a large nuriibcr of studies. The life span study
incidence data p 3 3 ] sugcst that risks are highest inyounger survivors, but there is little difference in excess
relative risk or excess absolute risk estimates by sex. Most
studies in which the data allow examination of temporal
patterns suggest that tllc excess rclative risks and thepeak within 3-10 years
excess absolute risks of lc~~kac~nia
of exposure and Ihen decline with time. For those exposed
as children, the risk aAer 25 years is very low. In the life
span study incidcncc data [P33] it was found that theternpowl pattern of the leukaemia excess absolute risk
depended on age at exposure, with the initial peak being
higher and the decrease more rapid among those expased
as children. Figure III illustrates this pattern. There has
been much speculation about whether or not excess
lcukaemia risks disappear 20 or more years a k r exposure.
The data fioni both the ankylosing spondylih study p,
L6] and the life span study suggest that elevated risks areseen 25 or niore years after exposure. The most recent
analysis of the data of the benign gynaecological disease
study [I121 suggests that risks for acute leukaemias vary
little over time among pcople exposed as adults. Thisfinding seenis to be consistent with the recent results of
the life span study [P33].
Although temporal variation in leukacmia risks
119.
followirig radiation exposure co~~lplicatesthe directcomparison of risk cstirl~atcs,these estimates can provide
some useful i~~fonnation
about riidiation-indud leukaemia
risks. In particuliir, the esti~rlatcsh n i the life spar1 study
incidence data F33] suggcst that risks per unit dose fromhigh doses (in excess of 3 or 4 Gy) are lower than thoseseen in studies of populations exposed to lower doses. The
results of detailed a~~alyscs
of leukaernia risks in thecervical cancer cohort IB12, B17j as well as a recent

ANNEX A: EPIDEMIOLOGICAI, STUD1[ESOF RADIATION CARCINOGENESIS

study of radiotherapy of the uterine corpus [C36] and, toa lesser extent, the life span study high-dose data suggestthat cell-killing tends to reduce excess leukaemia risks perunit dose following hgh-dose exposures. It is likely thatcell-killing can explain the relatively low risk estimates in
the ankylosing spondylitis study [D6, L.61 and in thechildhood cancer treatment study

m.

120.
Many analyses of leukaemia risks haveinvestigated the risks for leukaeniia subtypes. In general,
radiation exposure leads to increased risks for chronic
myelocytic leukaernia and for acute myelogenous orlymphocytic leukaemias. Tbere is no convincing evidenceof excess risk for chronic lymphocytic Ieukaemia. As adult
T-cell leukae~niais endemic at Nagasaki because of theunusually high prevalence of the HTLV-1virus. recent life
span study analyses considered the risk of T-cellleukaemia in adults but found no evidence of an elevatedrisk associated with radiation exposure. Ichirnaru andIshimaru [IS] also investigated this issue and found noevidence of excess adult T-cell Icukaemia risks among
survivors of the atomic bombing of Nagasaki. Subtypespecific dose-response functions considered in the life spanstudy incidence data [P33] show that the leukaemia doseresponse function is concave upward and that there isevidence of significant leukaemia risk at doses below
0 5 Gy. A joint analysis of the three leukaemia subtypes(chronic myeloid, acute myelogenous and acutc
lymphocytic) found that while there were statisticallysignificant differences between subtypes with regard to thetemporal patterns and the effects of age at exposure andsex on the excess absolute risk, there was no evidence ofsignificant differences in the shape of the dose-response
function.
121.
Numerous studies not included in Part XIl of
Table 8 and Figure II have investigated leukaemia risks inother groups of people exposed to radiation. Groups inwhich an association between radiation exposure andleukaemia risks has been reported include workers at the
Mayak facility in the Russian Federation [K23], adults
who received radiation treatment for non-Hodgkin's
lymphoma [G8, T4] and patients with cancer of theuterine corpus [B16, C8, C10, C14]. Radiotherapy for
Hodgkin's disease was associated with subsequent
leukaemia in some studies [K16, T8]but not in others. No
exleukaernia risks were found in a study of wonierl
treated for ovarian cancer [K15]. Leukaeniia was found tobe associated with postnatal exposure to diagnostic
radiation in several studies [G15, G18, P17, W] but notin others [B38, L4J.
A 30-year pilot study of aliriost 5,000
children estimated to have received 0.2-0.3 Gy during
cardiac catheterization failed to show a significant excess
risk of leukaemia, based on three obscrved cases
compared with 1.9 expected m 4 7 , S451. However, theexcess relative risk esti~natekom this sniall nunlbcr ofcases was 2.4, which is siniilar to that h s c d on data fmni
other studies included in the Table.

33

122
In summary, Uie incidence of acute leukaeniias orof chronic myelogcnous leukaernia exhibits strong
associations with l o w - J J 3 radiation exposure. Risks.
especially for those exposed as children, appear to peak 310 years after exposure and then decline with time. Thispattern is less pronounced for those exposed as adults, inwhich case there is little evidence for an early pcak in theexcess relative or absolute risk and the decline in risks, if
it occurs. is less pronounced. Recent work also suggeststhat the temporal pattern of risk of leukaemia following
radiation exposure depends on sex. While leukaemia risks
have generally decreased with time since exposure, small
excess risks persist 25 or more years after exposure(Figure m). Despite the strong evidence for radiation
effects on several subtypes of leukaemia, no study has
found evidence of an association between radiation
exposure and chronic lymphocytic leukaemia.

(m)hfdignant lyn~phoma( n o n - H d g b ' s )123. As summarized by Boice [B19], the evidence ofan association between radiation exposure and morbidityfrom non-Hodglun's ly~nphomais weak. Risk estimatesfrom a number of studies are presented in Part X m ofTable 8 and of Figure II. While none of these studics offer
convincing support of a radiation effect, tbe excess relativerisk estimates for several of the larger studics are similar
to those seen for other cancer types. The life span study
incidence data [P33] do not provide strong support for aradiation effectNon-Hodgkin's lymphoma has been considered124.
in a number of other studies for which it is difficult toestimate tile risk per unit dose. No evidence of an excess
of non-Hodgkin's lymphoma was found among persons
who received diagnostic x ray examinations for various
reasons [B38]. Data Gom the Oxford survey of childhood
cancers in children exposed prenatally to radiationsuggested an elevated risk of lymphoma p231, while astudy of twins in the United States provided no evidenceof an excess [I15]. Occupational studies of radiologists andx-ray technicians [M24, WlO] and of nuclear industry
worker; in the United Kingdom [K21] and in the UnitedStates [ G I 7 do not fiid sigruficant excess risk of nonHodgkin's lymphonla. In general. there is no convincing
evidence that non-Hodgkin's lymphonla is associated withradiation exposure.
(n)hlultipk nlyelon~aStudies of the survivors of the atomic bonibhgs
125.
in Japan and of people expwcd to radiation for medical
purposes provide little evidencc of an elevated risk ofniultiple nlyeloma following radiation exposure. Of thestudies included in Part XN of Table 8 and of Figure U,
only Uie mortality data of the metropathia haenio~bagica
study ID231 show a st;itistically significant excess risk of
myeloma. Significant excess myeloma risks were found in

34

UNSCEAR 1994 REPORT

earlier analyses of the mortality data [S7] and incidence
data [I131 of the life span study. In the most recent life
span study mortality report [R23], the point estimate of theexcess relative risk for multiple myeloma [23 (1.7-6.3)]
was higher than that for any other non-leukaemia cancer
type. The life span study irlcidence data [P331 involved not
only an extensio~i of the follow-up period but also a
review of the data for cach myeloma case. Althoughseveral cases included in earlier reports were excluded on
the basis of the reviews, the new life span study data set
indudes about 20 more cases than either of the earlier
reports. Persons with dose estimates in excess of 4 Gy andcases diagnosed as second primaries were excluded fromthe routine analysts. Tn this analysis the estimated excess
relative risk is much lower [0.4 (&1.7)1 and is notstatistically significant As noted in the analysis of theincidence data [P33] of the life span study, when both thesurvivors with high doses and the second primary cases
were included in the analysis, the point estimate of the riskincreased and approached significance.
126.
In an earlier review, Cuzick [ C B ]examined alarge number of cohorts arid concluded that radiation
exposure was associated with an increase in niycloma risk
About 40% of the cases i i this review were obtained Gom
the lifc span study. There llave bee11several recent studiesof the association between multiple niyelorna and exposure
to diagnostic x rays. In a casecontrol study of 208 casesorgani7ation,from a United States hciilth mai~~tenancc
Boice et al. [B38] failed to firid a statistically significant
association, but they noted that the risk appeared toincrease with the number of x-ray exposures. In a study of
399 mycloma cases and niatched controls, Cuzick and deStavola [C9]found no evidence of an association withdiagnostic x-ray cxposurcs.
127.
An association between low-dose radiation
exposures (average cun~ul;~tive
dosc 0.03 Sv) was initiallyreported for workers at ~ h cHanford site [Gu)],but later
studies cast doubt on this finding. Weak evidence of anincrease in risk oS multiplc myelonla with external dosc
was scen in the study of workers in the United K q d o n i
P(20, Ul]. In view of more recent Gridi~ysfor theJapancsc cohort [P33] and in the Hariford study [G16], an
association between radiation exposure and multiple
myeloma is not clear at this time.
3. 1)ifferunces by sex and by ethnic origin

The life span study data provide clear evidence of128.
sex diffcmnces in the excess relative risks. For solid
tumours, the exccss relative risk Sor females is gncrally
about twice that for males. However, the ratios ofnaturally occurriry age-spccific caricer rates in females inJapan arc about half thosc Sor niales, which implies thatabsolute excess risks are roughly equal for males andfemales. The joint analysis of the life span study niort;llity
data for three broad categories of cancer (digestive system,

respiratory system and other non-sex-specific solid
tumours) by Pierce and Preston [P20] adds support to the
hypothesis that sex effects in the excess relative risks
largely reflect differences in sex-spccific rates of normallyoccurring cancer.
129.
Sex-spccific estimates of the excess relative risk
and exccss absolute risk for the life span study mortality
data arid for tile life span study incidence data [TlS], as
well as sex ratios for each of these summary measures ofthe excess risk and for the background rates are given in
Table 9. For solid tumours as a group, the excess relative
risks for females are larger than those for males. However,in accordance with the hypothesis descnid above, theexcess absolulc risk sex riltios are generally closer to one
than are the excess relative risk ratios. Results for cancersof the liver and thyroid and for leukaemia appear to
deviate from Uiis pattern. For liver caricer the excess risks,both relative and absolute, a p p to be substantially lower
among fc~tialestllari among males despite the fact that in
the lifc span study, as in other populations, naturally
occurring liver caricer rates for males are higher than thosefor females.

In the life span study and other populations,130.
thyroid cancer occurs only about one third as oRen in
niales as in femalcs. Despite this difference in backgroundrates, sex-specific excess relative risk estimates are nots i g ~ f i c a ~ ~different
fly
The sex ratio seen for leukacmia
bckgrou~ldratcs is about the same as that seen for othercancer types, but the sex-spedfic excess relative risks are
similar.
131.
Because rnany of the medically exposed
populatiotls uscd in studies of radiation effects arc
coniposed wholly or priruarily of a single sex, theirifomlation on sex cffccts on radiation risk from
populalions other than the Japanese is limited. In the New
York tirica capitis study 1S4, S8], thyroid cancer excess
absolute risk estimates were found to be two to three times
grcatcr in fernalcs tl~ariie m;~lcs,and it was noted that Ulisratio is sirililar to the female-to-male ratio in backgroundrates. Tlic finding in the Israeli tinea capitis study [RlS]
were similar: a significant differcnce in the sex-specificexcess absolute risk estimate, but no significant differcnce
in the exccss relative risks. Sex differences were also
considered in the analysis of skin canccr in the Israeli
tinca capitis study p191. Despite differences in theestirnatcd risks per unit dose, sex effects in the two tinca
studies arc quite similar to thosc scen in Uie life spanstudy.
Since only 16%of Ihc me~nbersof the ankylosing132.
spondylitis study population arc females, there is little
power to dctec? sex differences in this population.
Howcvcr data prescntcd ill [D6]allow some comparisonsof sex-specific risk estimates. For cancers other thanlcukac~ni:~and colon caricxr there is no significant difference ill UIC esti~liatcdexcess relative risk pcr sievert forANNEX A: EPIDEMIOMGICAL STLlDlEiS OF RADIATION CARCINOGENESIS

males (0.15) and females (0.13) or in the estimated sexspecific excess absolute risk (5.8 cases per 10,000 PYSv
for males and 4.3 for females). Excess absolute risk andexcess relative risk cstimates for leukaemia among females
in the ankylosing spondylitis study arc about one third of
those for malts. However, since the mniber of leukaemia
cases among females is sniall (3 observed versus 1.8
expected), the standard errors arc large, so thesedifferences are not statistically significant
133.
Understanding how radiation risks differ between
ethnic groups is an important problem for radiation
research and protection. Although formal comparison isdifficult, the risk estimates prescntcd bi the last Section
suggest that there is no simple characterization ofinterpopulation variation. Relative risk summaries areemphasized in many studies; however, one niust be
cautious in applying these ri5ks to a population with very
different background rates. That there is no consistent,
simple characterizationof sex differences in radiation risks
suggests that ethnic or cultural diffcrences in radiation
risks are likely to be complex or difficult to distinguish.
Some diKerenccs in sensitivity to radiation by134.
ethnic origin have been found in the few studies that haveincluded substantial numbers of morc than one ethnic
group. For example, in the study of about 2,200 children
who received x-ray treatment for tinca capitis in New Yorkand a comparable group of 1,400 treated without x rays, 41
persons in the imdiated group had one or more basal cell
carcinomas of the face or scalp coinl~rcdwith only 3 inthe controls. Howcver. despite the fact that 25% of theirradiated group was black, all 41 ski11cancer cases werein whites [%I. In thc study of subjccLs inadiatcd in Israel
for tinea capitis, the risk per g a y of radiation-induced skincancer was internlediatc between the high risk found in the
New York whites and the absence of risk found in New
York blacks. In the Israeli tinea cxpitis study, a differenceby country of birth was also notcd, with subjects born inNorth Africa experiencing much greater relative risks ofradiogenic Icukaemia and thyroid calicer than subjects bornin Asia or Tsrael [R4, RS]. (It should be noted that all thesubjects born in Israel in this study had fathers born in Asia
or North Afiica.) However, country of birth did not appear
to modify the risk of radiation-related tuniours of the brain
and central nervous system [RlO]. The pssible effect ofthe prevalence of other carcinogenic agents is comidcred in
Section U.A.9. Risks of radiation-induced thyroid cancer in
Jcwish and non-Jewish subjects were rmmpared in the
study of the eKccts of thymic irradiation noted above[S35]. After adjushncet for the cii'ccts of sex and time
period, the risk of radiah~l-il~duccd
thyroid cancer was 3 5
tirncs higher @ = 0.01) in Jcwish than in non-Jewish
subjects. Thc populatio~iliving in Ihe contamiuated areas
along the Tccha River in UIC soulhem Urals, which
indudes both Russians and Tartars, who have different
natural cancer rates [K18], niight be able to provide usefuldata on ethnic diffcrcnccs.

4.

35

Effect of age at exposure

135.
Although the age range in populations used instudies of radiation e f k t s is oftcn rcstrictcd, data fromvarious studies provide a fairly consistent picture of theeffect of age at exposure on the risk of radiation-induced
cancer. As with sex effects, the nature of variation in risk
with age at exposure depends on whether one considers
relative or absolute risks. In particular, it appears that forsolid tumours at a given time a k r exposure, persons
exposed early in life have higher average excess relaliverisks and lower excess absolutc risks than thme exposed
later in life. This point is illustrated by comparing the
mortality data for the period of observations fiom tbe life
span study [It231 and the observed data from the ankylosing spondylitk study [D6] (Table 10). The data fromthe life span study are given for both sexcs combined andfor males only. Because of the high proportion of men in
the ankylosing spondylitis study, the life span study malerisks are likely to be morc comparable with the estimatesobtained in the ankylosing spondylitis study than are thepooled estimates of the life span study. Since these studies
involve different follow-up tunes and since the exposure
patterns both in the body and in h i e , as well as manyother Bctors, differed [U12], the excess absolutc risk
estimates are not directly comparable. Nevcrthcless. forleukaemia arid for all solid tumours these were comparedin the UNSCEAR 1988 Report [U2] (Annex F, Table 56)
and in [U12]. Considering the many diffcrences between
these studies, the agreement betwecn risk estimates is notunreasonable. DiKcrcnces UI time-averaged excess absoluterisks for differcnt age-at-cxposurc groups should be interpreted with caution because current data suggest that
excess absolute risks u~crcasewith increasing time since
exposure and because follow-up is incomplete for the
younger members of most c o h o a used in the studies ofradiation effects.
136.
An increase in average excess absolute risks withincreasing attained age would be a natural consequence ofa model in which the risk of radiation-induced cancer issimply proportional to background cancer rates. However,findings in the Israeli and New York tinea capitis studies[R19, %I, the Massachusetts tuberculosis fluoroscopy
study [B31] and a Canadian tuberculosis fluoroscopy study
w19] support tl~einfcrence drawn from the life spanstudy that solid tumour rclative risks are lager for those
exposed a t younger ages than for those exposed at older
ages. As discussed earlicr, for niost cancer types theexcess relative risk dccrcascs with age at exposure. The
large excess relative risk for those exposed as cliildrcn is
not easily interpreted but probably reflecLs, at least in part,the fact that background rates for those exposcd aschildren have been low for niost of the follow-up to date.
Kellcrer and Barclay [K12] recently notcd dlat a model inwhich the cxccss relative risk is allowed to dccrcase withincreasing attailled age wilhout any additional dependence
on age at exposure describes the life span study data about

UNSCEAR 1994 REPORT

36

as well as an age-at-exposure-dependent relative risk
model. Under the fitted Kellerer-Barclay attained-agedependent excess relative risk model, there is virtually no
differencx in attained-age-specific excess absolute risk
estimates. At the present time, data are complete only forthe older members of the population, so models are difficult to test Shimizu et al. [S7] noted a tendency forexcess risk estimates for solid tumours at a given attained
age to be greater for those exposed at younger ages thanthe corresponding estimatcs for those exposed at older
ages. This is an important question that needs to beconsidered further.
Studies of breast cancer incidence provide the137.
clearest evidence of age-at-exposure effects on the risk ofradiation-induced cancer. Table 11 contrasts data on ageat-exposure-specific excess relative risk estimatcs based onbreast cancer incidence data Gom several studies.
Although the numbers might suggest differences between
cohorts in the level of risk, in virtually every case thetime-constant excess relative risk estimates decrease withincreasing age at exposure. This is shown more clearly
when the data are plotted as in Figure IV. The studies
used for the plot are the life span study incidence data
[T15], the Massachusetts tuberculosis fluoroscopy study[B31], the New York acute post-parturn mastitis study[S9], the Rochester thymic irradiation study [H22], theSwedish benign breast disease study [Bl], the Stanford
Hodgkm's disease study v 2 ] , the United States study ofthe contralateral breast among wonicn who received
radiotherapy for breast cancer [B41] and the Canadiantuberculosis fluoroscopy study [M19]. All studies useddata on incidence, except the Canadian study, which
considered mortality data.
Despite the limited age range, data on thyroid
138.
cancer froxu the Israeli tirica capitis study [R15] and theMichael Reese tonsil irradiation study [S63] demonstrate
highly decreasing relative risks with age at exposure. A
similar pattern is seen among younger menibers of the life
span study cohort [A13, T15]. The life span study, whichis the largest source of data on adults, suggests that thyroid
cancer risks are quite small aniong those irradiated as
adults. Age-at-exposure-specificrisk estiniates for thyroid
cancer from the life span study, the Israeli tinea capitis
study and the Michael Recse study are compared inTable 12. The relative risks for some other cancer types
estimated for various age-at-exposure groups in the life
span study coliori are given in Table 13.

5. Prenatal exposureStudies or medical exposure to diagnostic x rays
139.
during pregnancy arc important because of the passibility
that the developing fetus may be more susceptible to the
carcinogenic effects of ionizing radiation than the adult or
the young child. The Oxford survey of childhood cancerj[B22, M25 S52] was the first (and is still the largest)study to find an association between obstetric x rays andchildhood cancer. Since its publication in 1958, numerous
other studies have reported similar relative risks ofchildhood cancer of about 1.4 without taking the fetal doseto the embryo and fetus into account These results arelisted in Table 14. Doubts about the causal nature of theassociation have been raised, however. They weresummarized in the UNSCEAR 1986 Report p 3 ] and,more recently, by others rM2.5, M33] and will be
discwed further below. It should be stressed that the poor
quality of the information on the dose to the embryo or
fetus and the possibility that some of the excess risk n~lght
be due to factors unrelated to the x-ray exposure preclude
an accurate estimate of risk per unit dose. Any such
estimates must be interpreted cautiously.
140.
Evidence of a causal association includes theconsistency of findings in many studies co~iductcdover a
period of 35 years [B22]. Case-control studies based on
personal intewiews were initially criticized because of thepossibility of response bias, but subsequent large studies
based only on reviews of obstetric rccords confirmed theassociation [M9]. The possibility of unidentified conditions
that select mothers for x-ray examination whose children
were destined to develop cancer was addressed in areanalysis of twin data within the Oxford survey ofchildhood cancers [M23, M32] and in two case-control
studies of twins m population-based tumour registry
regions in Connecticut [H3] and Sweden [R16]. Twins
were likely to have been x-rayed for reasons unrelated to
the niolhcr's health, such as to diagnose the twin
pregnancy or to determine fetal position before delivery,
and all three evaluations found an association between
prenatal x-ray exposures and childhood cancer. Controllirg
for maternal illness and drugs taken during pregnancy ui
the Oxford survey of childhood cancers did not change
appreciably the estinlates of relative risk w 2 ] .
Arguments against a causal association between141.
low dose. obstetric x rays and childhood cancer have beenraised. In laero exposure to the atomic bombings in Japan(triean uterine dose: 0.18 Gy p21) werc not linked to an
i~ic.rcasein childhood cancer. During the fust 14 years oElife, no leukaemias occurred in the in utero group, andonly two cancers werc diagnosed: one case of liver cancer
at age 6 years and one case of Wilms' tumour at age 1 4
years [J2]. The sample, however. is not large. Mast studies
of prenatal x-ray exposures found the relahe risk ofleukaemia to be 1.4 and the relative risk of all the majorgroups of solid tumourj also to be 1.4. The similarity
between these relative risks is strange, because thesecancers are lulo\vn to have dissimilar origins and very
different excess relative risks following postnatal
exposures. Such a correspondence is uncharacteristic of
any olher human or experin~entalanimal exposure, raisingquestions about biological plausibility [MZ,M33j.
Furtherniore, while Japanese children who were less than

ANNEX A: EPIDEMIOLOGICAL S 7 v l31ES OF RADIATION CARCINOGENESIS

1 0 years old when exposed to the atomic bombings wereat a very high risk of developing childhood leukaemia (14cases occurred), they did not develop any othcr childhood
cancers in excess [Yl]. Finally, it is noteworthy that
excess relative risks have been found only in case-control
studies. No cohort study has detected a significant increasem childhood cancer following prenatal irradiation [CIS,
D16,115, J2,05, R131; indeed, relative risks of about 1.0
or less have been found. The cohort studies can be
criticized, howcver, because of the small nunibcrs ofchildhood cases and associated low statistical power todetect an excess. Furthermore, one author later concluded
that there was a strong possibility that ascertainment wasincomplete in his investigation ID251 Despite thepresumed higher frequency of prenatal x-ray exposure
among twins than among singletons, cohort studies oftwins in Sweden. Noway, Finland, California andConnecticut havc also failed to find an increase inchildhood cancer, compared with the general population,and several studies report significant deficits [I15,R131.
The exact values of prenatal exposurc in the twin studies,
however, were not known, and the proportion irradiatedmay not have been as high as believed. Furthemlore, it is
not necessarily correct to expea twins to be at the samerisk of childhood cancer as singletons. Nevertheless, on thebasis of the above discussion the possibility of a causal
association must be recognbed, although quantification of
the risk remains uncertain.
If it is assumed that fetal doses from niedical
142
prenatal exposures were about 10 niSv, then the estimatedexcess relative risk per sievert derived from the various
case-control studies is roughly 40 for leukaemia and 40 forother cancers. This is in marked contrast to the prenatal or
postnatal risk in children derived from the atomic bomb
survivor studies. As noted above, there were no
leukaeniias in the prenatal group. Averaged over the first
35 years of follow-up (1950-1985), the life span study
mortality data suggest that the excess relative risks
per sievert in survivors of the atomic bombing who wereless than 10 years old when exposed are approximately 17
for leukaemia and 2 for other cancers [Sq. Other studies
of childhood irradiation find excess relative risks
per sievert for leukaemia that are generally smaller thanseen in survivors of the atomic bombings (Table 8, PartW IH21, R51.
143.
Despite the considerable uncertainty about themean fctal dose per obstetric examination, estimates ofrisk havc been made by UNSCEAR [U2,U4, U6] andothers p.K6, M22, M30, M32, S37]. These estimatesvary widely. Some estirnatcs [I;6] failcd to account for thedecrease in fetal dase per obstetric examination that
occurred over the years [M22]. Others relied upon theconccpt of dose per film [UZ] rather than the more
appropriate dose per examination, since more than one
film nlay be taken per examination [M30. M32). Someconsidered only fatal ar~dnot incident cancers; some were37

computed for the fust 10 years of life and others for the
first 15 years. One reccnt analysis of the Oxford sunrey ofchildhood cancers with adjustments for many of theprevious inadequacies in former computation indicates adecrease with year of birth in the excess absolute risk ofincident cancers over ages 0-14 years, perhaps corrcsponding, at least in part, to a decrease in fetal dose [M22].
The results are summarized in Table 15. Based on thesemore recent analyses of the Oxford survey of childhood
cancers, the excess absolute risk of mortality of all cancers
OE
for the first 14 years is about 5 10' SV-' W
144.
In the only study that has evaluated adult onset
cancers following prenatal exposure, Yashimoto et al. [YT
Y5] reported a statistically significant increased risk ofadult cancer among 1,630 prenatally exposed survivors of
the atomicbonibings followed through 1984. However, no
additional cancers occurred in the mast recent follow-up
interval (1985-1989), and although the point atimate of
the excess relative risk pcr unit dose remains quite high(0.9) it is no longer statistically significant [Yl] (95% CI:-0.12-3.81). The small number of cancer deaths (24) andthe limited follow-up during adult life contribute to theuncertainties in the result Further follow-up will clearly bc
important.
Studies of in ldero exposure have thus given a
145.
wide range of risk estimates, from relatively high risk toessentially srrlall undetectable risk, including (possibly)
none at all. Since there is no biological reason to assume
that the embryo or fetus is resistant to the effects ofionizing radiation, and in particular to leukaemogenesis,
the finding of a positive risk after appreciable doses is to
be expected. However, on the basis of present data theexact quantification of effects is subject to much
uncertainty.

6. Temporal pattern of radiation-induced
risk
The tcniporal pattern of radiation-relatcd ex146.
cancer risks is a clentral issue in radiation effects studies.
It is clear that temporal pattern for leukaemia and solidcancers differ greatly. Excess absolute risks for leukaemia
generally peak 3-10 years following exposure and decline
thereafter. Excess absolute risks for solid tumours maease
more gradually, possibly increasing monotonically for theentire lifetime following exposure. In the life span study
data, for a given age at exposure and sex, this inueasewith time in exccss absolute risk for solid tumours isrenlarkably proportional to the increase with age in the
background cancer rate for a given sex and age at
exposure. The data are most usefully and simply describedby time-con$tant excess relative risk n~odels,at least overlimited follow-up periods. This should no4 however, beinterpreted to mean that there is something fundamentallyand biologically true about such a model. In particular, it

38

UNSCEARshould not be uncxitically assumed that the model can beused to project beyond current follow-up for the life spanstudy or other studies. For the life span study this ismainly an issue for those exposed as children, who are
only now attaining ages at which the background rates ofcancer become large. Indeed, in the absence of complete
lifetime follow-up, the strong dependence of excess
relative risks on age at exposure may raise questions about
the adequacy of time-constant excess relative risk models.
It is important to realize that even if excess relative risk
decreased substantially with time, the exabsolute risk
would still increase, since background cancer risks
increase very rapidly with age. As has been noted inrecent papers [Kl2, P201, reasonably sinlple timeincreasing exccss absolute risk models can describe the life
span study data as well as constant excess relative risk
models. These absolute risk models often predict relative
risks that dccreasc with increasing time since exposure.
and they prcdic* smaller differences in attained-age-specificrelative risks than are predicted by timeanstant relativerisk models with age-at-expasure eEects. However, timeconstant absolute risk models, which were widely
considered in the past, do not fit current data and are nolonger useful for projection purposes.
147.
There is convincing evidence of an excess risk ofleukaeniia anlong survivors of the atomic bombings inJapan as eady as 1938 [F31 (all major subtypes except
chronic lymphocytic leukaemia), but formal description of
the risks is possible only Gom late 1950, when follow-up
of the f i c d life span study cohort began When the life
span study data for all age groups are considered together,
the relative risk was -greater during the fmt live years offollow-up than during later periods, and h e subsequentdecline in rclative risk is statistically significxnt [P33, S7].
However, the temporal pattcni of the excess lcukaemia
risk depends on both age at cxposure and sex and on thetype of leukaemia induced. In particular, as noted earlier
and illustrated in Figure IlI, leukaemia excess absoluterisks have a higher initial pcak and decline niore rapidly
for those exposed as children than do the excess risks fort h w exposed as adults. For a given age at exposure, thelife span study results also suggest that the inicial peakvalue for exccss absolute risk is lower and the decline lessrapid for women than for men. Indeed, the pooled
leukaeniia model described in p 3 3 ] indicates a slighlincrease in excess a h l u t e risk estimates with time since
exposure for wornen over age 40 at exposure. It is also
noted in p331 that a statistically significant leukaemia risk
was seen between 30 and 40 years after exposure.
148.
Studies of the clTccls of n~edicalirradiation on the
induction of leukaemia generally support the picture
emerging from the life span study data. The relatively
short interval between irradiation and the maximum
relative risk of radiation-induced leukaeniia has been
confimicd in several studics. For example, in the studies
of women irradiated for cervical cancer [B12], patients

irradiated for ankylosing spondylitis [D6] and children in
the relative
Israel given radiotherapy for tinea capitis F],
risk of leukaemia was at its highest within the first five
years after irradiation In the study of women irradiated fornictropathia haemonhagica p23, S121, the maximum
r c l a t ~ erisk occurred 6-10 years after irradiation. The
study of ankylosing spondylitis patients is also consistent
with the life span study cohort in finding a continued riskof radiogenic leukaeniia more than 25 years a k r
irradiation, although the relative risk was considerably
lower than at earlier periods (an excess relative risk of 1
for the period from 1 to 14 years after irradiation and 0.2
for 15 or niore years aflcr irradiation P I ) .
Although it is often stated that radiation-induced
149.
solid cancers are not seen for 10 or more years after
cxposure [DW,
S12], a radiation-related increase in solid
tunlour mortality is apparent in the life span study cohort
during the Grst five years of follow-up, that is at 5-10
years aRer exposure (excess relative risk per gray shieldedkcrma: 0.24 (90% CI:0.05-03) in 1950-1955 [Sq). This
small relative risk for all cancers, invdving a total numberof excess cases of about 15, cannot be furlher subdivided
into mealurgful risks for individual cancers. A moredetailed study of the types of cancer involved in theseearly deaths niight be useful, however. These excess
cancers were evident 5-10 years after the exposure in priorevaluations of the life span study, and early excess deaths
are also evident in the study of the ankylosing spondylitis
patients in the United Kingdom Attention has not previously been drawn to this period because the number ofcases and the excess risks are small. They are pointed out
now merely to indicate that the 10-15 year latency period
sonictimes quoted should be interpreted with caution. At
prcscnf the Committee corltinues to use a 10-year latency
period for solid tumours.
150.
With increasing time since exposure, the excess
absolute risk in the life span study cohort following agiven dose and within a given age-atexposure category
has iricrcased dramatically: by Eactors of 9, 3 and 10 forage-at-exposure groups 0-19, 20-34 and 35 years or more,
respectively, between the periods 1956-1%5 and 1 9 7 61985 (see Table 16). In contrast, the relative risk ofn~ortality from all cancers other than leukaemia has
rcn~aincdrelatively stable, so that when follow-up to 1985
is considered, nmdels that allow the c x m relative risk todepend on age at exposure and sex but not on time since
exposure are often used to describe the data [P3, P4, S7,
T151. However, as notcd earlier, there are alternative~iiodelsin which the excess relative risk b not constrained
to be constant in time that d e m i the data at least as
well as tinuwxmtant excess relative risk models with sex
and age-atexposure effects p 2 ] .
Although n~odelsin whicb the relative risk is151.
comtant with increasing time since exposure are used tosummarize the data on mortality Gom all cancers otherANNEX A: EPlDEhffOLOGlCAL STUDIF! OF RADIKIlON CARCINOGENESIS

than leukaemia in the life span study cohort up to 1985,
such models conceal some differenin the temporal
patterns of the radiation-related increase among different
age-at-expwurc groups. The report on life span study
cancer mortality through 1982 p4] noted statisticallysignificant differences in temporal patterns for survivors
with different ages at exposure. In particular, it was foundthat the excess relative risk tended to decrease in time forthose who were younger at exposure and to be constant orperhaps incrcase slightly for those who were older at
exposure. Pierce et al. [PU] carried out an extensive
examination of the more recent lifc span study mortality
data and concluded that the evidence for a decrease withtime in the non-leukacmia cancer mortality was based on
the experience of the youngest survivors. A similar conclusion was reached in the lifc span study solid tumour
incidence analysis LT1.51. Figure V illustrates agc-atexposure-specific relative and absolute risks based on thelife span study incidence data for 1950-1987 r 1 5 j . The
exccss relative risk model is linear in weighted dose (RBE
for neutrons = 10) and allows for sex-, age-at-exposureand time-since-exposure dependencies with different slopes
for those over and under age 20 years at the time of
exposure. While Lhe relative risks differ significantly withage at exposure, the decrease in the excess relative risk
with time is not statistically significant overall or for either
age goup. Excess absolute risks were computed as the
product of the fitted cxcess relative risks and the fitted
background mortality rates. While the excess relative risks
for females are about 40% greater than those for males,
the excess absolute risks for males and females are
similar. From this figure it can be s a n that despite a large
estimated decrease in the excess relative risk for survivors
who were less than 20 years old at the time of exposure,excess absolute risks have risen at about the same rate as
those for other age groups. The plots suggest that as the
youngest survivors reach the ages at which there arc rapid
increases in background cancer incidence, excess relative
risks may decline to those seen for older life span study
survivors.

A number of studies have paid attention to152
differences in tenipordl patterns of the excess relative risk
for specific non-leukaenua cancers. The life span study
mortality and i~lcidencereports [R27, S7,TI51 provide
trend tests for 111ost types considered. A statisticallysibwificant increasc in the risk with t h e (without
allowance for age-at-exposure effects) is reported for all
cancers other than Ieukaemia. Statistically significant timetrends were noted for one or two specific cancer types;
however, in view of the large nunibcr of tests carried out
and the relatively small number of cases at a particularsite, these tests fail to provide convincing evidence of asignificant variation between sites with respect to temporal
patterns of the excess relative risk. The BEIR V Committee [C12] developed separate models for cancers of thedigestive system, the respiratory system, the female hrcast
and other non-leukaemia tumours and elected to base risk

39

projections for cancers of the respiratory system and breaston models in which the excess relative risk decreases withincreasing time since exposure. However, a recent joint
analysis of the life span study data PU)] using the three
non-sex-specific, non-leukaemia categories considered by
the BEIR V Committee [C12] found that no evidence ofsignificant differences between these categories withrespect to age-at-exposure or ternpod patterns. It also
found that the category-specific, time-dependent excess
relative risk models used by the BEIR V Committee [C12]
did not provide a stahtically significant improvement in
fit relative to a simple, two-parameter, age-at-cxposuredependent, constant excess relative risk model. ib
described in the life span study cancer incidence reportr 1 5 ] , point estimates of a time trend for the breast cancer
data were negative, indicating a deaeasing excess relativerisk with time, but the decreases were not statisticallysignificant [P20].

In the study of ankylosing spondylitis patients the153.
relative risk for all cancers other than leukaeniia or coloncancer (40% of which are lung cancers) decreases
significantly with increasing time since exposure, with theestimated excess relative risk (0.07) for the period 25 ormore years after exposure being only about 20% of theaverage excess relative risk (0.38) during the preceding 20
years PI.Only for cancers of the oesophagus, liver,larynx, bladder and skin and for multiple myeloma were
the relative risks 25 or more years after exposure greaterthan those seen during the 5-25 year period, and only forcancer of the oesophagus was the e x m relative risk inthe later period statistically sqpficant The overall decline
in relative risk could not be attributed to the variation withtime in the types of cancer observed or to effects of age
at exposure or to inadequate ascertainment of death in theoldest age groups in the study. There was no evidence thatpatients who survived and remained in the study for 25
years after the initial treatment received doses that werelower than those who did not
A decrease in therelative risk for all cancers other than lcukaernia withh~creasulgtime following exposure has also been seen inthree groups of children given medical irradiation [L18].
In contrast, mults from the cervical cancer case-control
study suggest that relative risks for heavily irradiated sites,
which do not include the lung or the breast, tended to behighest 20 or more years after exposure [B21], although
there were few cases beyond 30 years after exposure.
154.
Temporal variation in excess relative risk
estimates has been considered in a number of ocher recent
studies of medically irradiated populations. In the mostrecent analysis of the data on breast cancer incidence
among wonien given frequent chest x-ray fluoroscopy in
Massachuseus, it was found that the risk remains high formore than 50 years p311. The relative risk of thyroid
tumours following thynius irradiation among inlints in
New York appears to decrease smoothly with increasing
titile since exposure 15 or niore years aftcr exposure, with

UNSCEAR 1994 REPORTJO

the relative risks for the pcriods 5-14, 15-24, 25-34 and>34 years since exposure estimated to be 11.0, 4.8, 2 0
and 1.8, respectively [SlO]. There is also a reduction in
relative risk with time in the tinea capitis study in New
York [L18]. Incontrast, the extended follow-up of subjects
in the tinea capitis study in Israel has found that therelative risk remains approximately constant for M yean
after exposure [R15]. Apparent differences such as theserequire reconciliation Additional statistical analyses of all
the available data may be helpful.
15.5.
In studies of the effects of exposure in childhood,no increase is seen in some types of cancer until the
population has reacl~cdan age when such tumours begin
to appear in the abscncc of unusual exposure to radiation.
For example, in the study of infants irradiated forsupposedly enlarged thymus, the fmt breast cancrr wasdiagnosed 2.8 years after irradiation [H22]. Similarly, inthe study of children in New York irradiated for tinea
mpitis the minhnuri~latcncy period for radiation-induced
skin cancer was about 20 years [SS]. However, theinterval between irradiation and the subsequent excess is
not always greater in children than in adults, especially fortulnours that are common in childhood and early adult life.
For example. in the study of children irradiated for tinea
capitis in Israel, tumours of the brain and nervous systembegan to appear only 6 years after irradiation [RlO].

7.

I k ~ s eresponse

In any discussio~iof h e dose response, tbe dose
1.56.
itself is of paraniount importanm, and because the life spanstudy is so important, the dosimetry of the survivors of theatomic bombings of Hiroshima and Nagasaki is especiallyrelevant The formal dosimetry scheme DS86 bas been
uscd as the basis of risk estimation in the life span study
since 1986.11 has generally been regarded as satishctory,
but recently some in~poriantquestions have been raised
about a potentially larger contriiution to the dose f m fastneutrons than was specified in DS86.This may have comeabout either because the RBEs for neutrons are very highat low doses. as has bcen suggested [R26,S331, or because
the presence of thcnilal r~eutrons[ S 6 ] is an indication of
p t e r nunibers of fast neutrons, especially at distances in
Hiroshima, than were allowed for in DS86.
When the DS86 was adopted (and even before
157.
that) physicists were aware of some discrepancies for both
Hiroshima and Nagasaki between thermal neutron fluxes
based on activation measurements and values derived fromthe fast neutron transport equations. These discrepancies
have become niore evident for Hiroshima (but not,ap$rcntly, for Nagasaki [Sn])with the nieasurcments ofin
Eu and '"EU in soil and measurements ofconcrete, both activated by thermal neutrons and reported
in [S6]. The ratio of measured thermal neutron activation
to that derived by calculation increases from less than 1 at

800 m or less from ground zero to about 2 at 1,000 m andabout 10 at 1,600 m. P e average DS86 fast neutronorgan absorbed doses for survivors at those distances are
1%2% of the gamma ray absorbed doses.) The origin of
these extm thermal neutrons that seemed to have beenpresent at Hiroshima is not known. If they come from fastneutrons not accounted for, presumably in the sourcc termfor Hiroshima, the total equivalent dose at greater
distances would need to be increased. Tbe m a e r is still
under investigation. In the meantime some calculations
have been made of the possible maximum impact of pdentially increased numbers of fast neutrons on risk estimates.
The increased equivalent dose would protmbly reduce therisk estimates by perhaps 10%20%, reflecting the fad thatthe change could not bc large at dase categories that
contribute most to risk [P15]. The fact that risk estimates
based on the incidence for all cancers at Nagasaki alonediffer very little from estimates based on that at Hiroshinia
and Nagasaki together would appear to m n f i that the
impact cannot be large. It should also be noted that adding
more neutrons at greater distances in Hiroshima will tcnd
to increase the disagreement between the two cities, which
DS86 iniprovcd over TD65.On tbe other hand, measurements of chromosome aberration hequencies (which do
not necessarily relate to cancer induction) induced by
gamma rays and a range of neutron energies were recently
used to rcanalyse aberration data for the survivors of theatorriic bombings. A neutron component of about 5% of
the absohcd dose was derived for Hiroshima, comparedwith about 2% in DS86 [S53]. Yet another recent reanalysis of stable chromosome aberrations among the atomic
bomb survivors at Hiroshima and Nagasaki examined the
dilTercnces between the two cities. It concluded that, in
DS86,the RBE for neutrons is very high or the neutrons
at Hiroshima have been underestimated or the gamma rays
at Nagasaki have been overestimated [S33]. The lastmentioned reason seems unlikely, since TLD (theniioluminescent dosimetry) measurements of the gamma rays
at Nagasaki confirm calculations.
Thus, evidence appears to be mounting that DS86
158.
does not fully account for the neutrons that were probably
present at Hiroshima, especially at the greater distances.
Prese~~tindications are that in analyses based on linear or
Ihiear-quadratic models, the overall redudion in risk
estimates resulting from ulcrcases in neutron doses would
not be large [Pl5]. There are also other features of DS86
that may, in time, require amendment. k include
correction for biases in risk estimates resulting fromrandom c m r s in individual dose estimates (paragraph 35)
and Ibr the effect of misclassilication of cancer on deathcertificates (paragraph 26), both of which would tend toincrease risk estimates [Sl].
There are a number of other important issues
159.
related to the shape of the dose-response fundon forradiation-induced cancer. These issues revdve around thedegree of curvature in the cancer dose-response function

ANNEX A: EPIDEMIOIDGICALSTUI3IES OF RADIATION CARCINOGENESIS

at low d m and the impact of cell-killing on the response,
especially at high doses. In a recent monograph, Kondo[K25] summarizes much of the experimental and epidemiological data on low-dose effects and offers acriticism of the linear no-threshold model of dose
response. The question of the shape of the dose-response
fundon at low doses is important since the doses ofinterest in radiation protection are often much lower thanthe doses in the epideniiological studies that conmiute
most of the information to risk estimates. Another issue,
which arises in part because of the neutron component of
the life span study exposures at Hiroshima, involves
description of the RBE of neutrons for cancer induction.
Experiments and epidemiological studies involving thedirect effects of law-LET radiation, e.g. the induction ofchromosome aberrations in lymphocytes, have generally
found that a linear-quadraticmodel describes the low-LET
radiation dose response better than a simple linear model.
These expcrirnents also indicate that cell-killing leads to aflattening of the dose-response function following highdose-rate exposures to hyh doses. While theseexperiments are crucial to an understanding of radiation
effects, it is important to remember that cancer induction
is a lengthy, multi-step process, and it is not clear that theresults for specific, observable cellular events should apply
directly to radiation-induced cancer risks (see UNS(=EAR
1993 Report P I ] , Annex E).
160.
Without a bettcr understallding of the issues
involved in transfeming risk estimates from one population
to another, comparison of risks for populations exposed todifferent doscs is of little use in clarifying the shape of thedose-response function. Thus,the most useful information
on dose response, especially at low doses, comes fromstudies of a given population with a range of exposuresand individual dose estimates. The lack of individual dose
estimates limits the usefulness of several large studies,including the ankylosing spondylitis study in the United
W d o m and the cervical cancer cohort study. There are,however, a number of important studies that do haveindividual estimates. These indude the life span study, thecervical cancer casecontrol study, the various tuberculosis
f l u o m p y cohorts, the benign gynaecological study andthe Israeli tinea capitis study.
161.
As was discussed in Chapter I, errors in individual dose estimates affect the nature of observed doseresponse relationships. As has been well documented [G4,J l , P3, P9], random errors in individual dose estimates
lead to a downward bias in the estimated risk per unit
dose. These crrors also distort the shape of tl~cobserved
dose-response curve. If, as is o k n the case in radiation
effects studies, errors in individual doses are roughly
proportional to dose, the apparent dose response will tend
to have less upward curvature than the true response.
162
Because of the interest in effects at low dose, theradiation effects literature is replete with two-group

41

comparisons involving lowdose groups and unexposedgroups; these comparisons are used to address the questionof the lowest dose for which effects can be detected. Suchtests should be interpreted with caution, since in mostcases the failure to detect effects is morc likely to be aconsequence of the lack of power of the test than anindication of the absence of an effect Furthermore,positive results can occur by chance only. While suchcomparisons should not be ignored coniplctely, once adose effect has been found, emphasis should be placed on
tests for departures from linearity (based on linearquadratic or spline models) rather than on specific dosegroup comparisons.
163.
Figure VI illustrates the relationship between
excess relative risk and weighted dose to the bone marrowor large intestine for mortality up to 1987 from leukaemia
and cancers other than leukaemia, respectively, in the life
span study cohort, using the DS86 dosimetry F11,P13,
R23]. For leukaemia, the estimates of excess relative risk
were derived from data for both sexes and all ages at
exposure. For cancers other than leukaemia, the estimatesof risk illustrated are those for a male aged 30 years at thetime of exposure; the risks for females in the life spanstudy cohort were roughly twice those for males. There isan apparent non-linearity in the dose responses forleukaemia over the range of doses, while the dose
response for solid tumours exhibits less curvature. The
issue of the non-linearity of dose-response curves from thelife span study for cancer mortality (and for incidence)
will be discussed further below.

164.
Because of concerns about the role of cell-killing
and the impact of errors in individual dose estimates on
the shape of the dose-response curves at high dcses, andbecause the life span study risk estimates arc primarily
used for effects at low doses, recent analyses of the life
span study data have oRen focused on individuals withshielded kerma of less than 4 Gy. Even when the analyses
are restricted to survivors with less than 4 Gy shieldedkerma, the risk estimates from the life span study arebiased by dosimetry errors. Calculations presented in [P9]suggest that bias corrections based on an assumption of
35% errors in individual dose estimates increase linear risk
estimates by about 6 % for leukaemia and 9% for cancers
other than leukaemia PI.
165.
Statistically significant risks for solid tumours in
the life span study (see Table 7) are presently seen only
above 0.2 Sv, i.e. the relative risks for solid tumours in thelower dose categories, namely 0.01-0.05, 0.06-0.09 and0.10-0.19 Sv, arc not significantly different from unity.
However, these dose categories all have positive nominal
risk estimates, and the slope of the dose responx for
doses lower than 0 5 Sv, while lower than the slope for all
doses up to 4.0 Sv, docs not differ significantly from it[S65] (see also Table 17). For soltle specific cancer sites,
point estimates of the excess risk are negative in some

1994 REPORT

low-dose categories, although not significantly so.
However, while a linear rclationship with dase for solid
tumours is consistent with the life span study data, otherdose-response models that exhibit curvature in the lowdose region cannot be ruled out.

166. The shape of the lifc span study cancer mortality
dose-responsc curve has been studicd in detail by Pierce
and Vaeth F11, PI31 for individuals whose shieldedkema was 0.4 Gy. Separate calculations wcre made forleukaemia and for all other canccrs, with and without anadjustment for the effect of errors on the estimated risks.
The f i n d models are of the form

ERR = p 8

) x p + OD*)

(12)

where D is the weighted dose assuming a neutron RBE of
10, a, and 1 5 represent~
possible sex- and age-atc~posure-dependent modifications in the linear risk perunit dose g, and 0 represents the degree of curvature in
the dose-response relationship. The reciprocal of 0 is theweighted dose at which the linear and quadratic parts ofthe dose-response relationship intersect and is often
referred to as the crossover dose. For cancers other than
leukaemia, 8 is estimated to be 0.1 SV-' or 0 2 SV-l,depending on whether or not the doses are adjusted for theeffect of errors. These values are not significantly different!?on1 zero. (A value of zero corresponds to a linear dose
response.) For leukaemia, 0 is significantly greater thanzero, with estimated valucs of 0.4 SV-I for unadjusted
doses and 0.8 SV-' for adjusted doses.
167.
The quantity 0 can be related to the dosereduction factor, which is the factor by which the slope ofa linear model should be divided to give the slope at low
doses, i.e. the linear tcnn in a linearquadratic doseresponse model. The valuc of the dose-reduction factor isequal to 1 + OD@ where Dg, which depends on the distribution of doses in the data under analysis, takes thevalue 15 for the life span study data p11, P13J. The
dose-reduction factor for mortality 6um cancers other than
leukaemia is estimated to be 1.2 or 13,depending onwhether dosinlctry errors are taken into account These
values are not significantly different fiom unity. The best
estimate of the dose-reduction factor for mortality fromleukaeniia is 1.6 if errors in the doses are ignored. Thisestimate incrcascs to 2 2 aRer allowance for the effect of
dosimetry errors. In addition to carrying out significancetests, Pierce and Vaeth [ P l l , PI31 calculated confidence
intervals for both 0 and the dm-reduction hctor. The
95% upper confidence linlits (one-sided) for the dosereduction factor for cancers other than leukaemia are 2 4
and 3.6 beforc and aftcr adjusLlnent for dosimetry errors,
respectively. The lower confidence limits were not given
explicitly but were less than 1.0 in both cases. The
corresponding upper 95% limits for leukaemia are 3.6 and6.0. Without adjustment for dosimetry errors tbe lower
bound is less than 1.0, hut after adjustment for dosimetryerrors the lower bound is 1.1.

168.
In the analysis of the life span study solid tumour
incidence data p15], the dosc response was found to beapproximately linear for survivors with DS86 welghted
doses between 0.2 Sv and 4 Sv, as can be seen in
Figures VI and W. Below 0.2 Sv, limitations of samples h e etc., discussed elsewhere, render quantificationdifficult. The pooled leukae~niadata ( F i e VI) p 3 3 ]wcre best d e s c n i by a linear-quadratic model withupward curvature. Although subtype-specific leukaemia
analyses failed to find evidcnce against linearity for acutelymphocytic or chronic rnyelogenous leukaemia, a joint
analysis that included these two subtypes along with acute
myelogenous leukaemia failed to find statisticallysignificant differences in the curvature for the threesubtypes. For all leukacmias considered as a single p u p
and for acute myelogenous leukaemia and chronic
myelogenous leukaemia considered separately, statisticallysignificant excess risks were seen at doses below 0 5 Sv.
For chronic myelogenous leukaemia and acute lymph*
cytic leukaemia, the slope of the dose-response function
below 0 5 Sv did not differ significantly from that forsurvivors with larger doses. Vaeth et al. [V14] presented
prclin~inaryresults of an analysis of cancer incidence dataon the shape of the life span study dose response forcancer incidence siniilar to that canied out for the
mortality data. The res~~llsof this analysis generally
parallel those for mortality described above [Pll, P13] andare shown graphically in Figure VIII. The difference incurvature between tlle solid tunlour and the leukaen~ia
dose-response functions is significant, and with a bias
correction for dosimetry errors, the estimated valuc of the
low-dose reduction factor for solid tumours is about 1.05
with a 90% confidence interval of 0.6-1.6. The corresponding leukaania point estiniate is 2 5 with a 90% confidence interval of 1.3-8.4. Figure VIII summarizes h eresulls for lowdose extrapolation factors for leukaemia andfor solid tumoun for both adjusted and unadjusted doses.
169.
Dose-response relationships have been consideredin several studies of the effects of medical irradiation.
Table 18 summarizes the results of an analysis of thedose-response rclationship for cancen and benign tumoursof the thyroid in the t i n a capitis study in Israel [RlS].
Relative risks increased appreciably even within thelimited range of thyroid doses received by study subjeds.
ARer adjustment for sex, ethnic origin and attained age,
the relative risk for cancers rose from 3.3 at the lowest
dose category (mean dose: 0.062 Gy) to 6.1 at the h~gbest
dose category (mean dosc: 0.214 Gy), while in a linear fit
the relative risks rose Goru 3.0 to 8.0 for the same dose
categories. For benign tumours, the dose-response curve
was not as steep. However, the adjusted relative risks still
increased from 1.1 to 4 5 , while the fitted risks increased
from 1.9 to 4.0. It should be notcd that while some aspectsof the dosirnelry in tlle ti~icacapitis study in Israel seemto be sound, the values of the doses to tbe thyroid glandand to the breast may have gnatrr unczrtau~tiesthan thoseof the doses to organs directly in the x-ray fild. In addi-

ANNFX A: EPIDEMIOLOGICAL STUD1[ESOF RADIATION CARCINOGENESIS

tion, it is possible that the irradiation of the pituitary gland
may intluence the response of the thyroid, and in the tinea
capitis study in Israel the pituitary doses were high.
170.
Dose-response relationships for breast cancer
incidence have also been examined in several tuberculosis
fluoroscopy studies. In neither the Massachusenq incidence
study [I3311 nor the Canadian mortality study [MI91 wasthere any evidence of sigmficant non-linearity in the dose
response. The data in Tables 19 and 20 descriie the dose
response seen in the Massachusetts data. The original
Canadian tuberculosis fluoroscopy data set included only
women treated in Nova Scotia. The most recent report
w 1 9 ] included data on women treated in other provinces
as well. Both the average doses and the estimated excess
relative risk at 1 Sv were lower for women treated inother provinces than for those treated in Nova Scotia. Thisfinding had been interpreted as suggesting a non-linear
dose response. However, results descriied in [MI91indicate that a linear dose-response model that allows fora region-dependent slope Gts significantly better than alinear-quadratic model that does not allow for regional
differences. Adding a quadratic term to the linear model
did not improve the fit, however, and a pure quadraticmodel was found to fit significantly worse than either the
linear or linear-quadratic alternatives.

If one examines the studies at hlgher doses in the171.
risk comparison tables presented earlier in this Chapter, thecomparisons often suggest that estimates of the risk perunit dose at higher doses are low. These apparent lower
risks are consistent with the idea that cell-killing at h y hdoses reduces the pool of cells at risk of developing
cancer. As noted earlier, it is dillicult to separate cellkilling from the effects of errors in individual dose
estimates in the life span study data when both probably
contniute to a levelling off or downturn at higher doses(Figure VI). However, a number of studies of medically
exposed populations can provide information on the effectof high doses. Extensive analysis of data on leukaemia
following exposure to high doses has been carried out
using the cervical cancer patient data [B8,B121. For thispopulation, in wbich the average total bone marrow dose
was about 7 5 Gy. it was found that relative risks
increased with dose for doses up to about 4 Gy but
decreased at higher doses. The breast cancer data fiom theacute post-partum mastitis study in New York [S9]suggest that relative risks levelled off at doses in excess of
3 Gy and appeared to decrease after about 5 Gy (seeFigure IX) In the study of patients treated with x rays forankylosing spondylitis in the United Kingdom, the excess
absolute risk of leukaemia was found to vary erraticallywith radiation dose over a range of mean marrow doses
up to about 7 Gy [S13), but a model with linear andquadratic terms for the leukaemia induction rate andexponential cell-killing at higher doses fitted the datareasonably well. In a case-control study of cancers
following radiotherapy for childhood cancer, it was found

43

tl~atexposures as high as 60 Gy were associated with ahigh risk of thyroid cancer [T5]. While there was nodownturn in the risk at high doses, the results are notinconsistent with a hypothesis that the slope of the dase
response is lower at high doses than at low doses (relative
risks in the dose ranges <2, 2-10, 10-30, 30-60 and%O Gy were 1.0,75,7.6,9.2 and 12.0, respectively) [B8,T5]. The first cancers in this study were neumblastoma(seven cases), Hodgkin's disease (five cases), Wilms'
tumour (four cases), non-Hodgkin's lymphoma (fourcases), brain cancer (two w e s ) and other cancers (threecases). Finally, the excess relative risks of leukaemia
derived from highdose studies (7 Gy or more) such as
those involving breast radiotherapy [C24] tend to yield
lower values of excess relative risk per unit dose than forthe survivors of the atomic bombings, indicating aprobable effect of cell-killing. Thus the evidence for cellkilling effects varies, but it is probably a factor in mosthigher dose responses and may even have an impact atlower doses [Sl]. Furthermore, cell-killing effects mayvary according to the site of cancer considered.
172.
The life span study is the only important epidemiological study in which people were exposed to both
gamma rays and neutrons. It is not possible to compute
useful estimates of the neutron RBE from the life spanstudy data because of the high correlation between gamma
and neutron doses. However, it has been shown p 3 ] thatrisk estimates are not greatly affected by changes in theassumed (constant) value of the neutron RBE for RBEs in
the range 1-20 because the neutron doses are small.
Although the life span study data do not allow precise
estimation of the RBE, it has been demonstrated [TI51
that RBE values developed on the basis of experimental
data on chromosome aberrations [Dm, S53] do not fit
with those derived from the data for solid tumours of thelife span study. This lack of fit is not related to the valueof the limiting RBE of neutrons; instead, it results fromthe fact that there is curvature in the gamma d m responsein the experimentally derived chromosome aberration
dose-response models but not in the solid tumour
incidence or mortality data.
8. Fractionation

173.
In many situations of interest in radiation
protection and risk estimation, such as those involving
occupational or diagnostic exposures, the risk associatedwith any given total dose to a particular organ may
depend on the dose rate and on the number of fractions inwhich it is delivered. Exposures in almmt all of thestudies considered in Section IIA were received at highdose rates. However, the degree of hadionation varied
from a smgle fraction for the survivors of the atomic
bombings in Japan to a few firactions for patients given
thymus irradiation to large numbers of hctions for the
exposure of radiologists and patients with pulmonary
tuberculosis receiving air lung collapse treatment.

44

UNSCEAR 199-1 REPORT

than those in other populations of women with similar
background rates, e.g. the acute post-partum mastitis series
in New York, whose radiation exposures involved relatively high dose rates and little Gadonation. Anotherposible factor is that of better ascertainment in the wellstudied Nova Scotia population as well as more precise
dosirrietry because all the patients faced the x-ray tube.

174.
Some tuberculosis patients were monitored withchest fluoroscopy every two weeks for five years or
longer. Their exposures are thus much more comparable
to mrrent oc~upationalor diagnostic medical exposuresthan the experience of persons exposed to hlgh smgle
doses. Two major studics of tuberculosis patients havebeen carried out. One included 4,940 women who weretreated in Massachusetts betwccn 1925 and 1954 andfoUowed for an average of 30 years [B31]. Among 2,573
women who were examined an average of 88 times. themean breast dose was 0.79 Gy; 142 breast cancers wereobserved compared to 107.6 expected based on incidence
rates for the general population used as controls. In
contrast, no excess was found for 2,367 women treated byother means and not regularly irradiated (87 observed
versus 100.9 expected). The relation between dose andrelative risk of breast cancer was consistent with linearity
up to 4 Gy, and for those aged 20 years at exposure theexcess relative risk at 1 Gy was 0.70. This is lower thanthe value seen for breast cancer incidence in the life spanstudy, which is about 2 (Table 11). However, much of thedifference in these excess relative risks may be due to thelarge differences between background breast cancer
incidence rates in the United States and those in Japan.
ARcr allowing for these it is likely that the excess absolute
rates in the Massachusetts tuberculosis fluoroscopy cohorts
and the life span study arc quite similar. The variation inexcess relative risk with age at exposure and time since
exposure was also consistent with that seen in the life spanstudy (see Table 11).

The breast is not the only organ for which there are176.
human data on the effect of d m fractionation. There has
also been an opportunity to examine fractionation effects inpatients inadiated in infancy for supposedly enlarged
thymuses [SlO]. Patients mated with x rays in Rochester,
New Yo&, h r n 1926 to 1957 and their unimdited
siblings were contacted by mail questionnaire and pertinent
medical conditions were verified with tbe doctor or thehospital noted on the questionnaire. To eliminate thepassibility that cell inactivation at high d m might mask
any sparing effect of dose Gactionation, h e tiactionation
analyses were limited to the 2,358 subjects with total thyroid
doses less than 6 Gy.Analyses were carried out of the dme
per fraction, the number of fkadons and the interval
between hctions; the rcsults are sumnlarizerl in Table 21.
The cxccss absolute risk of thyroid cancer per gray wasnunierically greater in the group with tbe lowest dose per
fraction, but there was 110 significant trend in e x a s sabsolute risk with increasing nulnber of tiactions or with ageater interval between fractions. A Cox regression analysis
ronsidering rel;~tiverisk also rcvealed no evidcna: of asparing effect of any of the three fractionation variables.

175.
The second study of tuberculosis patients given
Uuoroscopies included 31,710 wonien treated at sanatoria
in Canada betwecn 1930 and 1952 w19]. About a quarterof these women received doses of 0.10 Gy or more, andtheir relative risk of death from breast cancer as comparedwith those exposcd to less than 0.10 Gy was 1.36 (95%
CI:1.1 1-1.67). Women in Nova Scotia experienced excess
relative risks per unit dose that were approximately threetimes higher than wonien in other provinces. The data areconsistent with a linear dm-response model, and therelative risk appeared to decrease with increasing age at
exposure. The BEIR V Coninlittee [C12] reported that thetemporal pattern of the relative risks was similar to thats e n in the life span study. However, r a n t analyses ofthe life span study incidence data with five to w e nadditional years of follow-up IT151 suggest that relative
risks have remained Lirly constant in the survivor cohortThis seems to differ frotii the findings reported in v19]and [C12]. Within the Canadian cohort, differences in theslopes of the dose-response curve for women treated in
Nova Scotia and in the other provinces is puzzling. Although the rliean numbers of fluoroscopic exposures weresimilar, the dose rate was niore than an order of magnitude greater in Nova Scotia than elsewhere v 1 9 ] , and apossible explanation suggested by the authors is that thismight be a dose-rate effcct. While this may be the case,the estimated relative and absolute risks are much higher

The effect of fractionation on subsequent lung17.
canccr risk has also been examined in patients withtuberculosis [D14, H431. In an extension of tbe Massachusetts study, 6,285 patients examined by x-ray fluorascopy anaverage of T7 times during lung collapse therapy were
followed for an average of 25 years. The average dose to
the lung was 0.84 Gy. B a s 4 on United States nationalmortality rates, there was no evidence of hcmscd mortality
h m lung cancer (SMR: 0.8, based on 69 deaths). It is by
no meam clear that national rates in the United States forlung cancer form an appropriate basis for calculating
expected numbers for patients who are undergoing lungcollapse therapy. In addition there was no evidence of adose-response relationship despite a wide range of doses tothe lung. Lung cancer risk did not vary with time since
exposure or age at exposure, and adjustment for smoking
habits and the amount of lung tissue at risk did not
appreciably modiQ these findings. 'lbe authors interprctcd
tt~esedata as suggcsthy that, in contrast to breast cancer,
Gactionakd exposures as expericnccd by this cohort may beless effective in causing lung cancer than a single exposureof the same total dose. This interpretation is supported by arecent study on the Canadian fluoroscopy expcricnces, inwhich no excess of lung cancer was detected after
Gactionated exposures averaging about 1 Gy [H433.
However, a small risk of lung cancer was found afterradiotherapy to the breast 1120, N8].

ANNEX A: EPIDEMIOLOGICAL STLn:IIES 01: RADIATION CARCINOGENESIS
Another group who received highly fractionated178.
high-dose-rate x-ray expasures is formed by radiologists
and other medical x-ray workers. The results of studies ofindividuals in these groups were reviewed recently by
Carpenter [C25] and are summarized in Table 2 2 For
many ofthe studies, dosimetry infomiation is very limited.
However, although many of the early radiologists had
occasional single doses that were high enough to cause
overt radiation effects w4],those joining the profession
after the introduction of radiation protection guidelines
would have been exposed repeatedly only to low-dcsc x
or gamna rays. For most of the groups listed in Table 22,
guidelines were introduced during the 1920s (for example
in 1921 in the United Kmgdom), although they were notissued until the late 19% in China w14]. Thus, theincrease in mortality with increasing time since entry into
the profession seen in the United Kmgdom study forradiologists entering the profession after 1920; the excesses
in the study in the United States for those entering in
1940-1969; and the results obtained for recent follow-up
periods in the studies in Japan and Denmark provide
strong evidence of the carcinogenicity of very highly
hctionatcd exposures to low-dose low-LET radiation
However, there are reasons to interpret these studies withsome caution In particular, the dose estimates are crude.
and it is possible that some workers, especially thase
employed before radiation protection guidelines had been
introduced, mlght have received high doses. In addition,
since there is no internal comparison group, results an:based on comparison with national rates. Furthermore,some of the differences may reflect factors other thanradiation, such as alcohol or tobacco.
179.
A tendency for higher relative risks among those
exposed at younger ages is also apparent among diagnostic
x-ray workers in Chixia [W141, who received hlghly
fkactionated exposures. In this group the relative risks forleukaemia and thyroid cancer decreased with increasing
age at first employment (see Table 23). The relative risks
for all cancers combined, exclusive of lcukaeniia, washighest among workers Erst employed before the age of
20 years, but otherwise the data suggest linie variation in
relative risks across age-atemployment categories. The
highest relative risks for breast cancer were seen amongt h a e aged 3 - 2 9 years at first eniployrnent Some of thevariation in relative risks by age at first employrnent may
be attriiutable to the varying length of follow-up or thedifferent total doses accumulated to date for the different
groups. (Average observation times ranged from 19.9
years among workers who were lcss than 20 years oldwhen they started work to 11.7 years among those who
were 40 years old or over.)9.

Joint effects of radiation and other agents

180.
The effects of joint exposure to more than one
carcinogen can bc studied in depth only if detailed information can be obtained on the extent of exposure to each45of them. There are relatively few examples where suchinformation is available for human populations. However,detailed studies have been canied out of cigarette smoking
and asbestos exposure in relation to lung cancer among
insulation workers, and also of cigare~esmoking andalcohol consumption in relation to cancers of the oralcavity, pharynx, oesophagus and larynx, and these havebeen summarized by tfie International Agency for Research
on C a n m PI.In these examples, it was dear that the two
carcinogens did not act independently and that the relative
risks among those exposed to both were similar to the
product of the relative risks observed among individuals
exposed to only one or the other. Further evidence thatdifferent carcinogens do not act in isolation fiom one
another is provided by the increase in excess a h l u t e risks
with increasing age seen in many populations exposed toradiation in adult life, presumably the result of cumulative
causative factors (see Section IIA4).
The topic of joint effects was last reviewed by
181.
UNSCEAR in 1982 [U4]. Since then, a number of additional studies have been published. Several epidemidogicalsurveys, conducted between 1963 and 1970, asrertained
cigarette smoking status for various subsets of the life spanstudy cohort. In interpreting the results of analyses basedon these studies it should be noted that current cigarettesmoking status, rather than smolung status at the time of
the bonibing, was ascertained and that cigarettes werevery scarce in Japan towards the end of the Second World
War. Prentice et al. P I 2 1 examined cancer mortality
among 40.498 such individuals in relation to total T65DR
rddiation dose and cigarette smoking habits at the time ofthe survey. Thirty-three per cent of lightly exposed persons( ~ 0 . 1 0Gy) were cigarette smokers as compared with 41%
of heavily exposed persons (>1.00 Gy). There thus appears
to bc some potential for cigarette smoking habits toconfound and distort the relationship between radiationdose and cancer mortality in the life span study cohort In
the analysis of Prentice et al. p12], the at-risk period foreach individual extended fiom the month of the k t
sunrey in which the individual took part to the end of
1978 or to death, if this occurred earlier. Cancer mortality
for sites reported at that time to be related to radiation
exposure [Kg] was found to be still significantly relatedeven after taking into account cigarette smoking status. An
exception was multiple niyelonia mortality, where there
were not enough cases to allow study. Further analyses
using relative risk models that were either multiplicative or
additive in the two exposures (smoking and radiation) or~iiodelsthat took more general forms were also carried out
for some sites of cancer. Persons heavily exposed to bothcigarette smoke and radiation were found to havesignificantly lower cancer mortality than multiplicative
relative risk models would suggest for all non-haematologic cancer, stomach cancer and digestive cancer otherthan stomach cancer. Surprisitigly, the relalive risk
Cunction for those cancers appeared not only to be
submultiplicative (i.e. the excess relative risks were lower

1993 REPORT

than those predicted by the multiplicative relative risk
model) but also to be. subadditive (i-e. the exccss relative
risks were less than those predicted by an additive model).
The lung cancer relative risk hmction, on the other hand,
could not be said to be either multiplicative or additive,
but there was no suggestion that it was subadditive.
182
A further study of the joint effects of radiation
exposure (,T65DR) and cigarette smoking status during the
1960s in relation to lung cancer incidence up to the end of1980 was carried out by Kopecky et al. [K8] m a subsetof the life span study cohort The data were found to bewell fitted by a model in which the excess relative risk
was the sum of two components:(a) a radiation-related term that increased with decreasing
age at the time of the bombing;(b) a smoking-related term that increased with daily
cigarette consumption, as measured at the beginningof follow-up, and with attained age.

In this model there was no s@cant synergism between
the effects of radiation exposure and smoking, suggestingthat the two factors might combine to increase the relativerisk of lung cancer in an additive rather than amultiplicative fashion. The data are illustrated in Figure X.
One consequence of this is that the radiation-related
relative risk is greatest anlong non-smokers and decreases
with increasing tobacco consumption. Adjustment for theeffect of smoking by means of this additive relative risk
model substantially reduced the apparent sex differencesin the radiation-related relative risk of lung cancer, since
few women and most men were smokers. Thus, dZferencesin smoking habits between men and women may largely
account for the generally higher relative risks seen for
women than men in the life span study cohort for cancxrs
other than leukaemia (see Section TIA3 and Table 9).
183.
The interplay between risk of radiation-induced
skin cancer and degree of skin pigmentation was discussed
in Section II.A.3. In the study of children in New York
irradiated for tinea capitis [S8], the skin cancer risk wasparticularly pronounced on exposed areas such as the Bce.
The excess skin cancers occurring on the fringe arcas of
the face were estimated to yield a risk about 4.6 times
greater than that estimated for skin cancers on the hairy
scalp [Ha]. This strongly suggests that exposure toultraviolet radiation has increased the carcinogenic effectof the x rays on the face, relative to their effect on thescalp, which is protected from ultraviolet rays.
Another factor that alters the risk from radiation
184.
was obselved in women given radiotherapy for breasth~flan~mations/infectiomassociated with childbirth orlactation [S9, W]. Even after controlling for age attreatment, women who were irradiated shortly after theirfirst childbirth subsequently had a greater rxccss risk ofbreast cancer per g a y than women who were irradiatedafter their second or later pregnancies. This finding
complements those of other epiden~iologicalstudies andconErms that age at first childbirth seems to be an

important risk-modifying Bctor for breast cancer [Lll].

185. Patients with cancer treated with radiation andchemicals provide an o p p e t y to evaluate whether thetwo exposures interact in causing secondary leukaemias and,possibly, other cancers. In the largest series to date [CB],patients with breast cancer who were treated with radie
therapy and alkylating agents were found to have a slgnificanfly higher risk (RR = 17.4) of developing leukaemia than
women receiving radiotherapy alone (RR = 24, mean doseto bone mamow: 75 Gy) or alkylating agents alone (RR =10.0). Ninety secondary leukaemias were evaluated in acohort of 82,700 women High doses to bone marrow in thechest wall appeared to add appreciably to the risk ofleukaemia after chemotherapy. Other smaler studies
disagree regarding the risk of leukaemia after combined
therapy. Two studies of Hodgkm's disease p 6 , T8]
conduded that the leukaemogenic effect of chemotherapy
was not affected by concomitant radiotherapy; anotherreported the opposite p8]. Breast cancer risk following
Hodgkin's disease treatment with radiation may have beenenhanced due to chemotherapy with alkylating agents [H2].
Evaluations of patients with ovarian cancer have consistently
reported that combined chemotherapy and radiation is not
associated with a greater risk of leukaemia than &em+
therapy alone [G6, Kl5j. Previous studies, however, were
somewhat limited by small numbers of leukaemia cases incach treatment category and by the absence of a large
comparison p u p of patients who received neither radiation
nor chemotherapy. In the peptic ulcer study [Gll] it wasnoted that radiotherapy in combination with surgery greatly
enhanoed stomach cancer risks. The authors, while acknowledging that this may have been a chance finding, h p
thcsimd that the joint effect m@t be h e to radiation
damage to flie stomach mucasa.
The possible joint effeds of oncogenic v h w
186.
infection and radiation exposure are of increasing interest
As discussed in paragraph 120, reccnt incidence data on
adult T-cell leukaemia (ATL) in the sunivors of the atomic
bombings show no association between ATL and radiation
exposure p33], providing evidence for a lack of joint
effecl~betwan radiation exposure and HTLV-1 infection,
whicll is endemic in Nagasaki. Those liver cancers found to
be incrcascd as a result of radiation exposure from theatomic bombings are largely hepato-cellular carcinomas, forwhich heptitjs-B, and also recendy hepatitisC, v i m
infections are niajor risk factors in certain areas, including
Japan The possible interaction between radiation and hepathat hepatitis-B virus infedion is suggested by find*titis-B surface antigen positivity is increased in persons
e x p c d to 1 Gy or more, although exposed and nonexposed individuals seem to be infected by the virus eguallyfrequently [K24].

187.
Additional interactions of interest involve theinllucnc~of reproductive history. oestrogen levels and otherANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

known breast cancer risk factors on the risk of radiationinduced breast cancer. Recent studies P I 9 1 found noevidence of such interactions. The hypothesis that there
exists a small population of women with a genetic susceptibility to radiation-induced breast c a n m (suggested to
explain the large relative risks for early onset breast cancer
among women m the life span study who werc exposed as
children [L20Dshould be further investigated.

188. An excess of leukaemia has been reported amongchildren who received therapy with pituitary grcwlh
hormone. Of the six cases of leukaemia, five had also
received radiotherapy. Gowth hormone is known to stimulate proliferations of both normal and leukaemic human
lymphocytes The authors speculate that growth hormone
might be a promoting agent in the subgroup of children who
had been exposed to therapeutic radiation p19].
The joint effects of radiation and othcr factors on
189.
the induction of cancer is an important and interesting
subject that can only be addressed through epideniiologicalstudies. Unfortunately, epidemiological studies will rarely
have enough power to provide definitive answers to thesequestions.

10. Lifetime risk estimates
190.
Lifetime risk estimates are often used tosummarize radiation risks. A number of issues must be
considered in the definition and presentation of lifetime
risk estimates. These issues, which were discussed in
Chapter I of this Annex and which are reviewed at lengthin [TI41 and [Pll], include the following:(a) the model(s) to be used to descnbe the excess
incidence or mortality for the cancers of interest;@) the method of projecting risk beyond the period forwhich follow-up data are available:(c) the background age- and sex-specific death rates forthe reference population;(d) the definition of lifetime risk to be used:(e) the method of transferring risks estimated for one
population to another population
Lifetime risks have generally been summarized by a single
number that represenis the experience of a specified
population following a specific type of exposure. While
having such a number is convenient, simple summaries
can conceal substantial variation with regard to sex andage at exposure. Estimates stratified by age at exposure
and, when necessary, by sex are provided in the analysis
in this Section.

(a)Mdek for Lifetirue risk estiniatiun

191.
Despite the large number of studies of radiationand cancer in humans, the life span study remains themain source for developing models for risk estimation.

47

While it would be useful to be able to develop models
from other studies for use in lifetime risk estimation, thisis not usually possible owing to insufficient sample size,
the highly non-uniform distribution of doses to different
tissues within an individual, inadequate dose estimates insome cases, short follow-up periods, and, in many cases,
the restrictions on the age and sex distribution. The risk
estimates to be computed here are based on models that
describe the life span study data.
Since the temporal pattern for radiation-induced192.
leukaemia differs markedly h m that for othcr cancers, it
is appropriate to consider separate models. One could also
attempt, as was done by the BELR V Committee [C12], todevelop separate models for specificnon-leukaemia cancer
types or categories. While differences in excess risks for
specific cancer types undoubtedly exist. observed
differenoes in these risk estimates largely reflect samplinge m r s because of the relatively small number of excess
cancers of specific types. The results in p20], discussed
in Section K k 7 , show that even using the broad
categories in the report of the BEIR V Committee [CI2].
it is difficult to detect statistically significant differences
between the category-specific dose-response models. The
non-leukaemia risk estimates presented below werc
computed using a model developed from the pooled life
span study data on solid nunour cancer mortality for 19501987 [R23].
193.
With the exception of the youngest survivors,
excess relative risks for solid tumours in the life spanstudy have so far been remarkably constant during thefollow-up. Even for those exposed as children, a constantrelative risk model provides a useful summary for thecurrent follow-up, and the primary question for this p u p
irivolves the projection of risks beyond the current
Sollow-up period. The much larger excess relative risks todate for those exposed as children compared with adults
rnay be due to the low background cancer rates for the
younger group thus far, or it may reflect a general increasein the sensitivity of younger survivow This uncertainty
suggests that a reasonable approach to the estimation ofage-at-exposure-specific lifetime risks would be to use atime-constant excess relative risk model for a period
corresponding to the current follow-up period and to pay
explicit attention to the effects of different methods for
projecting the risks beyond the current follow-up period.
This approach makes clear the extent to which
extrapolation uncertainties vary with age at exposure. In
particular, for those cxposed after about 30 years of age
little extrapolation is currently necessary, while for the
youngest survivors the choice of projection method has anappreciable inlpact on lifetime risk estimates. Because it isbased on more adequate summaries of the current data,
this approach to the assessment of sensitivity to n~odellingis preferable to comparing lifetime risk estimates based onmodels of the-constant excess relative risk and timeconstant excess absolute risk.

48

UNSCEAR 1994 REPORT

194.
While it seems reasonable to use time-constantexcess relative risk models to descnhe the current life spanstudy solid tumour data, life span study excess relative risk
estimates exhibit statistically significant variation with age
at exposure and sex. Thus, the basic models used in the
lifetime risk computations for solid tumours are excess
relative risk models of the following form:

excess absolute risk for two doses at several different
times after exposure. This model differs fiom the model
used in the UNSCEAR 1988 Report p 2 ] in that it allows
for a non-linear dose response and for temporal variationin the excess risk Since chronic lymphocytic leukaemia israre in Japan, this model should be taken as a model forleukaemia risks excluding chronic lymphocytic leukaemia.

where a, is the sex-specific linear excess relative risk
per sievert, D is the weighted dose, e is the age at
exposure in years and 0 is an age-at-exposure effect
Separate models were used for cancers of the oesophagus.
stomach, colon, liver, lung, urinary bladder, breast, wary
and all other sites as a p u p . Parameter estimates are
based on models fit to the life span study mortality data
for the period 1950-1987 P I . These estimates, along withpardmeter estimates for a single model as in equation (13),fitted to the data for all solid cancers as a group are given
in Table 24. Excess relative risks predicted by these models
for selected ages at exposure are given in Table 25.

197.
Data on the survivors of the atomic bombings inJapan and fiom other exposed populations indicate thatsignificant increases in deaths fiom leukaemia can be seen
as early as two years after exposure. Since follow-up of
the life span study did not begin until slightly more than
five years after exposure and excess risks, especially foryounger survivors, were very high at that time, it isimportant to allow for some cxcess ieukaemia risk during
the period from two to five years after exposure. For themain lifetime risk computations (deaths per unit population
pcr sievert) it was assumed that the excess rate for theperiod before 5 years after exposure was equal to half thefitted excess rate at 7 5 years after exposure.

195.
The solid tumour lifetime risk estimates presented
below were computed using cancer risks obtained bysumming the estimated instantaneous site-specific risks. A
10-year latency period was assumed in the computations
for all solid tumours. This approach differs in two respects
from that used for the primary risk estimates in the
UNSCEAR 1988 Report [UZ]. Fit, the excess risk
models allow explicitly for the effects of sex and age at
exposure. Secondly, site-specific risk coefficients wereused for all fstimates

Leukaemia excess risks exhibit substantial sex1%.
and age-at-exposure-dependent variation with time since
exposure on either a relative or an absolute scale. In thecomputations summarized below, the pooled life spanstudy exccss absolute risk model for leukaemia from 1950
through 1987 p33] was used. The excess absolute riskfunction for this model with units
PYSV)-' is givenby the following equation:

where D is the weighted dose in bone marrow (neutron
RBE = 10). t is the time since exposure (years), 8 is 0.79
SV-', and a arid p are sex- and age-dependent parameters(for age at exposure of 0-19 years: a = 0.33 SV-l,0 =0.17 per year for males and a = 0.66 SV-l, P = 0.07 peryear for females; for age at exposure of 20-39 years:
a = 0.48 SV*', = 0.13 per year for males and a = 0.66
SV-l, p = 0.03 per year for females; for age at exposure of~4.0years: a = 1.31 SV", p = 0.07 per year for males anda = 264 SV-', 0 = 0.03 per year for females). This model
involves a non-linear time-dependent dose-response
function in which the cxccss absolute risk depends ontime, sex and age at exposure. Figure HI illustrates the
temporal pattern of the excess risk for men and women ofdifferent ages. Table 26 contains point estimates of the(b)

Projection methocls

198.
Three projection methods were used to examine
the impact of different assumptions about the future courseof tiic solid tumour excess risk In all three, the excess
relative risk values predicted by the model given above
were assumed to hold for the period from 10 to 45 years
after exposure. For the first projection method, it was
assumed that fie excess relative risk would remain
constant throughout the life of the survivor. The second
arid third methods h t l l involved the assunlption that forsurvivors who were less than 45 years old at exposure theexcess relative risk would decrease linearly starting 45
years after exposure. Under the semnd method the rate ofdecrease was defined so that when the survivor reached
age 90 years the excess relative risk would be equal to theavenge excess relative risk for a survivor who was 50
years old at cxposure. For the third method, the rate ofdecrease in the exccss relative risk was defined so thatwhen the survivor reached age 90 years the excess relativerisk would be zero. Figure XI illustrates the projection
procedures for survivors aged 10, 30 and 50 years at thetime of exposure. Life span study leukaemia risks are
small and appear to be decreasing for the youngest life
span study survivors. Thus, there appears to be no need toconsider alternative projection methods for leukaemia
risks.
(c)Tmsfer of risk estimates
between populations

Despite the relatively large quantity of data on
199.
radiation risks, the question of how to apply risk estimatesderived for one population to a different population
remains unanswered. T l e data that are available suggestthat there is 110 simple solution to this problem. For

ANNEX A: EPIDEMIOLOGICAL STUD1ES OF RADIAllON CARCINOGENESIS

example, the limited data (Table 8, Part 11) on stomach
cancer following radiation exposure in different
populations suggest, albeit weakly, that relative risks may
be more similar than excess absolute risks in populations
with disparate background stomach cancer rates. The
BEIR V Committee [C12] concluded that for breast cancer
the excess relative risks are more similar than the excess
absolute risks. However, although no new parallel analysisof the various breast cancer data sets has bee11 reported,
based on the data presented here (Table 8, Part wI),thecurrent evidence for such a conclusion seems lesscompelling than it appeared to be five years ago. In
particular, the updated life span study breast cancer data
do not suggest that age-specific relative risks are
decreasing with time. Also, the time-averaged excess
relative risk per sievert for women exposed at any age at
exposure is larger than that in most of the other breast
cancer cohorts. The observation that sex differences insolid tumour excess relative risks are generally offset bydifferences in sex-specific background cancer rates mightsuggest that absolute risks are more siniilar than excess
relative risks.

200. Since current data provide no clear evidence of
how risks estimated for the life span study should beapplied to another population, lifetinie risk estimatespresented in this Annex are calculated only for a specificJapanese population, which in itself requires a transferfrom the actual population exposed in 1945. Age- and sexspecific national death rates in Japan in 1985 [J5]from allcauses, all cancers except leukaemia and leukaemia are
givcn in Table 27. Although age-at-exposure-specificestimates are emphasized. population average lifetilne risks
were computed using age- and sex-weyhting based on the1985 Japanese population It should be noted that calculations of risk in other populations have been niadc in the
UNSCEAR 1988 Report [U2] for the populations of
Puerto Rico and the United Kingdom using a multiplicative transfer, and the results for lifctinie risk based on
multiplicative projection were quite similar for all three
countries, differing by only 20% overall. ICRP VlO],
in a more extensive comparison of five populations(including the Chinese population) with rather different denlographic characteristics, used both a multiplicative and an additive transfer [L12]. Lifetime risks
varied at most by a factor of 2 for the multiplicativetransfer (less for additive transfers) and by only 30%
if the Chinese population was not included. Thus theeffects of transfer between populations, while very
important, arc not so large for total cancer risk. For
the transfer of risk in individual organs, as ICRP
points out, some much larger differences can arise[IlO]. Results presented in paragraph 212 indicate thatsex-specific risks for individual sites can differ greatly
within a single population. even when there is little
difference in total excess cancer risk. These results
underscore further the difficulties of transferring risks
between populations.

(d)

49

Methds and results

201.
As noted in Chapter I, issues related to the d e h i tion of lifetime risk have received considerable attention inrecent years w 4 2 , P11, T141. Thomas et al. [TI41
identified three different nleasures of lifetime rick thathave been used in recent analyses. The lifetirnc riskspresented later in this Section are estimates of the risk of
exposure-induced death (REID) given as the percentage ofthe exposed population (paragraph 51)- Since the lifetime
risks given in the UNSCEAR 1988 Report [U2] wereexpressed per 1,000 people, they should be divided by 10
to allow comparing them with those given here. When
comparing UNSCEAR lifetime risks with those in thereport of the BER V Committee [C12], it is miportant tonote that the estimates given by the BEIR V Committee
are based on a different measure, excess lifetinie risk.
While risk of exposure-induced death and excess liretinle
risk estimates are sinlilar for leukaemia, estimates of therisks of exposure-induced death for solid tumours are
10%20% greater than excess lifetime risks, as discussed
in Chapter I. The two risk measures arc compared, using
the same underlying population and cancer death rates, inTable 28.

201
Another important issue regarding lifetime risks
concerns the lack of linearity in d m . Even if theunderlying risk model is linear in dose, the risk of
exposure-induced death is a non-linear function of dose.
Because of the non-linearity, simple linear extrapolationfrom values at 1 Sv underestimates the value at 0.2 Sv by
about 15% for the young but less at older ages. The
results at both doses are given in Tables 29 and 30.
203.
Loss of life expectancy is an important supplement to risk of exposure-induced death or excess lifetime
risk, since neither of the last two measures adequatelyreflects the time at which the excess cancers occur. In
other reports, the loss of life expectancy hq been definedas the expectcd life-shoflening per exposed individual.
This is ordinarily a very snlall number, since it reflects
both the life-shortening among those dying of radiationinduced diseasc and the small chance of this occurring. In
lhis Annex loss of life expectancy is expressed as theaverage yeas lost per exposure-induced case (YLC),
which is calculated as the average years lost per exposed
individual divided by the risk of exposure-induced death.
The UNSCEAR 1988 Report [U2] provided estimates ofthe years lost per 1,000exposed individuals. The years lostper exposure-induced case corresponds to those estimates
divided by 1,000 multiplied by the risk of exposureinduccd death, which is the expected number of exposurcinduced deaths per 1,000 persons.
204.

Tables 29 and 30 present the age-at-exposurespecific risk of exposure-induced death and years lost per
exposure-induced case for leukaemia and solid tumours,
respectively. following acute exposures of 0.2 Sv andH)

UNSCEAR 1994 REPORT

1 Sv. These lifetime estimates were calculated using thesex- and age-at-exposum-specificmodel d e s c n i d earlier.

Since sex difircnces between the estimates of risk of
exposure-induced death and years lost per e x p u r e induced case for solid tumours were small, single averaged
values are given for cach age at exposure. For example,
under the assumption of constant relative risk, the lifetime
risk of exposure-induced death from solid tumours for a
person exposed to 0.2 Sv at birth are 5.4% and 6.2% formales and females, respectively, for an average of 5.8%
(Table 30). Conesponding estimates of sex-specific years
lost per exposure-induced case arc 1 2 5 and 16.3 years foran average of 14.3 years (Table 30). Sex differences areeven snlaller for those exposed later in life. Table 31
contains estimates for each of the three projection methods
outlined above. As can be seen, risk estimates for thealternative projection methods are 20%30% lower thanthose given for the constant relative risk projection. For
the lifetime risk of leukaeniia (Table 29). no projection isneeded (see paragraph 198).

205. The constant relative risk projection predicts that
6% of those exposed at early ages to 0.2 Sv will die fromradiation-induced solid tumours, with an average of about
14 ycars of life lost per case (Table 30). Estimates of riskof exposure-induced death and ycars lost per e x p u r e induced case decrease with increasing age at exposure,falling by age 60 years to about 13% and about 8 years,
respectively. Comparison of the estimates for the threeprojection mcthds shows that the values of the risk of
exposure-induced dcath based on declining relative risk
projections for those exposcd early in life are about half
those predicted by a constalit relative risk projection andthat the effect of the projection method decreases for those
who were older at exposure. In contrast to risk of exposure-induced death, the years lost per exposure-inducedcase increase when declining risk projections are used.
This is to be expected, since the number of exposureinduced cases later in life is reduced by the declining risks.

206. The estimates of leukaemia risk are given
separately in Table 29 for males and females. The
estimates of risk of exposure-induced death for those
exposed to 0.2 Sv early in life are about 0.2% for males
and about half of that for females. The large values ofyears lost per exposure-induced case are a consequence ofthe short latency period and the generally decreasing risk
with time since exposure. Because of the interaction ofage at exposure with sex arid with time in the leukaemia
risk model, estimates of the risk of exposure-induced deathfor persons aged 40 ycars at exposure are higher thanthose for persons exposed at age 35 years. Risks of
exposure-induced death at 1 Sv are greater than would be
predicted by proportionality with 0.2 Sv risks because of
the non-linearity in the lcukacmia dose-response functionused for these projections. As is the case for solid
tumours, estimatcs of years lost per exposure-induced caseare relatively independent of dose.

207.
Population-weighted risks of exposure-induced
dcath and years lost per exposure-induced case have been
calculated for comparison with the estimates given in the
UNSCEAR 1988 Report. The comparisons are given in
Table 31. For a 0.2 Sv exposure, the risk estimate of
exposure-indud death and the years lost per exposurei n d u d case for solid tumours are 2 4 % and 11.2 years,
respectively. The corresponding estimates for a 1 Sv
exposure for solid tumoun are 10.9% and 11.6 years. The
age distribution of the 1985 Japancse population was used
to provide weights for averaging the age-atexposurespcilic risks. The most relevant estimates from the
UNSCEAR 1988 Report IIJ2] are those calculated using
the n~ultiplicativcrisk projection model with age-specificrisk coefEcicnts. The 1 Sv estimates (from Table 62 ofAnnex F of the UNSCEAR 1988 Report [U2D arc 9.7%
and 11.4 years.

208. A non-linear dose-response model is used for thepooled leukaenlia data. For a 0.2 Sv exposure, the estimateof risk of exposure-induced death from leukaemia andyears lost per exposure-induced case an: 0.16% and 3 4years for men and 0.11% and 27 years for women. The
corresponding cstirnatcs of risk of exposure-induced death
for a 1 Sv exposurc am 1.3% for men and 0.9% forwomen. The estimates of ycars lost per exposure-inducedcase are uncharged from tlre values at 0.2 Sv. The sexaveraged estimates in the UNSCEAR 1988 Report [U2] foran expxure of 1 Sv arc 1% and 26 years. The estimatednumber of years lost per exposure-induced case in the
UNSCEAR 1988 Report is less than the number given inthis Annex, because the earlier estimates did not adequately
allow for time-dependence in the lcukaemia risks.
For all cancers, solid tumours plus leukaemia, the209.
risk of exposure-induced death is 2 5 % after exposure to
0.2 Sv and 12.0% after exposurc to 1 Sv. The lattcr
number compares with the value of 10.7% determined forthe risk of exposure-induced death after exposure to 1 Gy(organ absorbed d m ) in the UNSCEAR 1988 Report p 2 ](see Table 31).
210.
The solid tumour risk model used for the
calculations presented above is for fatal cancers. An excess
relative risk model for first primary tumours in the life
span study is also available [W].With this model itwould be possible, in principle, to calculate lifetime
incidcncc risks based on lnethods similar to those used
above. In particular, solid tumour incidence rates could besubstituted for Lhc nlorlality estimates and used together
with death rates for all causcs other than solid tumours inthe basic calculations. The main practical problem incarrying out sucll computations is tl~cnccd for appropriate
age- and sex-specific cancer incidence rates. In many
countries, such rates arc not readily available.
As has been noted several times in thc Annex,
211.
models for site-specific risks have large uncertainties, andANNEX A: EPIDEMIOLOGICAL SlWDIE:S OF RADIATION CAl7CINOGENESIS
the differences in site-specific risks that are seen are
greatly affected by sampling errors in the data as well as
by details of the models chosen. With these caveats in
mind, a number of site-specific risk estimates have been
determined and are listed in Table 32. The non-leukaemia
estimates were calculated using site-specific time-constantrelative risk models for the life span study data in whichrisks were allowed to depend on age at exposure and sex.
As with the carlier estimates in this Annex, these models
were applied to 1985 Japanese site-spccific cancer
mortality rates. Age-at-exposure-specific REID estimates
were averaged using weights determined from theJapanese population. The life-table computations forlifetime risk estimation involve deaements in the
population at risk at any age that are due to the exposure.
Thus, the lifetime risk for a given site depends on whether
other sites have been exposed. For example, the lifetime
risk for lung cancer will differ according to whether the
exposure is to the lung only or to the whole body. The
results presented here Fable 32) assume that only thetarget organ was exposed to 1 Sv weighted dose.

51

types Indeed, site-specific analyses are all that can becanied out for many studies. There is strong evidence foran association between radiation e x p u r e s and many solid
tumours, especially for the most common solid tumour
types such as those of the lung, stomach and female
breast. However, there is littie or no evidence of radiationinduction for such cancers as those of the cervix, uterus
arid gall-bladder or for chronic lymphocytic leukaemia. In
between these two extremes is a middle group of tumour
end-points for which indications of excess risk occur insome studies, possibly or even probably suggesting an
association with radiation exposure, but the results fallshort of statistical significance. In those epidemiologicalstudies of solid tumours in which adequate dosimetric data
are available, the dose-response function for all solid
tumours taken together is consistent with linearity atweighted doses between 0.2 to 4 Sv.

214.
The pattern of excess leukaemia risks differs fromthat seen for solid tuniours in several respects. First,
excess risks are seen within 2-3 years of exposure.
Secondly, leukaemia excess risks (relative or absolute),
212
Table 32 provides sex-specific and averaged
especially in those exposed as children, appear to peak andestimates of the REID for several sites and also values ofthen decline with the passage of time. Despite the decrease
the average years lost per exposure-induced case 0.
in risk with time, current data do not indicate that exccss
Although specific values in this Table should beleukaemia risks ever disappear completely. Again, as withinterpreted with caution, it is interesting that while the total
the solid tumours, it is important to note that there isrisks for each sex are similar, there are shiking differcnccs
virtually no lifetime follow-up data on persons exposedin the distriiution of the site-specific excess risks for men
under the age of 20 years. Although investigated in
and women. The differences for liver and stornach seemnumerous studies, there is no evidence that radiation
particularly noteworthy. The large liver cancer risk for
exposure increases the risk of chronic lymphocytic
men reflects the unusual sex difference in the relative risk
leukaemia.
for this site. Overall, however, given the uncertainties inthe data and some arbitrary aspects of choice of models,
215.
Results for malignant lymphomas and multiple
the site-specific risks of Table 32 should be regarded as
myeloma are Its clear than those for leukaemia or solid
representative of a given choice of models and data rather
tumours. Studies of Hodgkm's lymphoma following
than as definitive of the relative values of risks forradiation exposure have consistently failed to demonstratedifferent sites.
an excess. The data on non-Hodgkin's lymphoma
incidence in the life span study (P33] provide no clear
evidence of an effect, although some evidence of an
11. Summary
excess is seen in the mortality data of the ankylosing
spondylitis study [D6] and the peptic ulcer study [ G l l ]213.
Studies of the carcinogenic effects in humans ofbased on comparisons with population rates. Recent data
external exposures to low-LET radiation delivered at h g hfrom the life span study [P33] suggest that evidence of andose rates, even though varying widely in scope andexccss of n~ultiplemyeloma is not as strong as had been
quality, provide convincing evidence that these exposuressuggested in earlier analyses of the mortality data. At thisincrease the risk of cancer in many organs and tissues oftime there is no conclusive evidence of an increased
the body. In particular, for some cancers other thanincidence of lymphoma and myeloma following high-dose
leukaemia, lymphomas and multiple myelonla, it seems
low-LET radiation exposures.
reasonable to conclude that excess risks occur within about
5-10 years after exposure and that the elevated risks
216.
In this Annex site-specific risk estimates for acontinue to increase. on an absolute scale, for most or all
number of sites and for leukaemia from a number ofof the remaining lifetime. This must be qualified by thestudies have been presented in a common format. It has
fat? that virtually no lifetime follow-up data are yet
been emphasized that direct comparisons of the simple
available on populations of persons exposed before the age
summary estimates must be interpreted with cautionof 20 years. Analyses of data on radiation carcinogenesis
because of differcnccs in the nature of the expmures, thein humans, including the analyses presented in thisquality of the dose estimates, the demographic
Chapter, often focus on results for specific solid tumourcharacteristics and the length of follow-up time. However,1994 REPORT

some overall impressions can be formed based on the risk
estimates provided in Table 8. These estimates highlightthe central role of survivors of the atomic bombings inrisk estimation The life span study is the most comprehensive single sourn: of data on the effects of external
exposure to high-dose-ratc low-LET radiation and one of
the few studies that has enough excess cases along with abroad range of doses and individual dosimetry and withvariability in age, age at exposure and sex to support
efforts to model dose respo~~re,effect modification andtemporal patterns of risk Despite the importance of thesurvivors of the atomic bombings in the characterizationof the risk of radiation exposure, studies of other radiationexposed populations help to clarify, confinn or qualify thefindings of life span study. More importantly, they provide
information on issues that cannot be addressed directly by
the Japanese data, in particular the effect of chronic lowdose and highly fractionated exposures and the variabilityof risk in different populations. Also there are a few
cancers, including leukaernia and breast and thyroid
cancer, for which a number of useful results from studies
other than the life span study arc available. For mostcancers, including such important ones as the stomach andthe lung, the number of useful results is more limited. For
some other cancers, such as. canccrs of the prostate,pancreas, cervix and testes, as well as Hodgkin's diseaseand chronic lymphocytic leukaernia, no estimates ofradiation risk exist because no study has convincingly
related these sitcs to radiation exposures. While the resultsthat are available do not sugest great disparities between
risks in the life span study and those in other studies,
questions of the comparability of risk estimates have notand, unfortunately for most sites, cannot be addressed indetail using current epidemiological data.
The Committee has attempted to derive roughly
217.
comparable risk estimates of excess relative and absoluterisks per unit dose for a broad range of studies. Although
there are many problems with the calculation, interpretation and comparison of the simple summary measuresused here, the Commitkc feels that presenting estimates inthis way is useful because it moves away from an overemphasis on the results of statistical tests of the hypothesesof no effect and examines instcad the differences andsimilarities of risk estimates for different cancer types invarious studies.
The Committee has derived lifetime estimates of218.
the risk of mortality fro111 all solid tumours and fromleukacrnia from the data of the life span study for theperiod 195G1987 using tliree different projection procedures. Although the metllodology diKers somewhat fromthat used for the lifetirnc risk estimates of mortality
presented UI the UNSCEAR 1988 Report [U2], whichwere based on data for the period 1950-1985, comparison
is possible for the constant relative risk (or multiplicative)model. The risk of mortality from all radiation-induced
cancers is slightly higher in this Annex: 120% following
expasure of 1 Sv. comparcd with 10.7% in the UNSCEAR

1988 Report p2]. Using alternalive projection methods thatallow for uncertainties in the projection for those exposed atyounger ages, the lifetime risk estimates are 20530%
lower. Lifetime risks are also derived for induced cancer inu~dividualorgala and tissues, but since these depend on
many assuniptions, some of them arbitrary, they are muchless precise than the total lifetime risk of fatal cancer.

B. LOW-DOSERATE EXPOSIJRES
219.
For more than 30 years, estimates of the numberof radiation-induced cancers that might be expected tooccur among populations exposed to external low-LET
radiation received at low dose rates have been based onrisk coefficients derived from data on populations
irradiated at high dose rates. Usually these studies havealso been at high doses, although some, such as thesurvivors of tile atomic bombings, cover a very broad
range of doses with many persons exposed at low doses
as well. In general, low-dose studies have been less usefulfor risk estimation because they are of low statisticalpower, and many of the published studies have severe
limitations. Uncertainties in epidemiological low-dosestudies can be due to several factors, including inadequate
dosimetry, narrow dose ranges, inadequate or inappropriate
controls and extraneous effects from confounders that arepotentially more troublesome when the effect being
detected is expected to be small. However, by far the mostconsistent problem in low-dose studies is their lack of
power, i.e. the number of persons involved, the length of
the follow-up and the doses to which they were exposed
may collectively be too small to have any chance ofdetecting a radiation effcct

In recent years, several reporls have appeared
220.
from which some estimates of risk may be e m c t e dThese reports, which present data on persons
occupationally exposed to radiation at low dose rates, on
the effect of varying levels of terntrial gamma-ray
exposures and on the effect of exposure to environmental
releases, are summarized below. In order to havereasonable power to detect any radiation-related effects,
such studies niust be very large. However, even if theselow-dose studies are not sufficiently large, they may be
indicative of an effect and perhaps even able to provide
r-mde risk estimates, but with wide confidence limits. It
seems quite unlikely, however, that studies of lowdoserate expmures to low-LET radiation will be able toprovide a means of examining detailed patterns of risk,such as variations with age at exposure, time since
exposure and other rclcvant parameters.
1. Occupetiond studies
For the purpose of quantifying risk, occupational
studies offer the most proniisc of providing informative
results because of the large nuniber of s u b j a a who have221.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

been exposed occupationally in many countries and whose
exposures have been individually monitored and recorded.
By far the most important occupational data come fromdetailed observations on radiation workers in the nuclear
energy industry who have received cumulative doses
varying fiom less than 1mSv to over 1 Sv in the courseof many years. Observations have thus far been publishedon about 20 groups of workers, totalling well over 100,000
subjects, mostly men, in the United Kmgdom, the UnitedStates, Canada, India and the former USSR [AlO, B4,B5,
B27, B30, C3, C16, C22, D10, D22, D26, F11, F16, G3,
G5, G9,G16, G17,G19,H17,H32,H45, K20, K21,K23,
M15, M41, N1, N2, N3, N4, N6, P24, R1,S14, W3, W7,
W20, W21, W22, W23, W241. Total mortality in thesegroups was generally less than that in the general
population for all men in the same ages over the same
period in the country in which they worked (seeTable 33). This establishes that they did not suffer a grosshazard, such as has been observed in coal miners andasbestos workers, but it does not exclude the possibility
that a small or moderate number of radiation-induccd
deaths have occurred in these groups. As noted inparagraph 27, it is quite common for mortality rates inselected populations to differ from general population
rates, and m such situations it is important to make use ofinternal comparisons to the extent possible and to try tounderstand and explain any differences between the
exposed cohort of interest and the population from which
the rates were drawn. In occupational studies, working
populations are often observed to have lower age-specificdeath rates for all causes and for cancer than the general
population. This is known colloquially as the healthy
worker effect An important source of uncertainty in someworker studies is possible confounding due to exposure toother workplace agents, such as chemicals, that may
elevate the cancer risks.
To assess the effects of radiation exposures in222
these occupational groups, it is necessary to makecomparisons within the industry, comparing the mortalityof workers (mainly men) by level of occupational radiation
exposure. This has been done in the United States forworkers at the Hanford plant [G5,G161, the Rocky Flats
nuclear weapns plant [W71 and the Oak Ridge National
Laboratory (C3, W211. the Mound facility [W23. W24].
the Oak Ridge Y-12 plant [C22] and the United Nuclear
Corporation p 2 ] ; in tbe United Kingdom for workers at
the Sellafield plant [S14], the Atomic Energy Authority[B4,Fll], the Atomic Weapons Establishment w e ] andthe National Registry of Radiation Workers
and inCanada for workers at Atomic Energy of Canada Ltd.
[G3. HG]. Results of studies that have provided risk
estimates are summarized in Table 34. It should be notedthat in most of these studies a large number ofassociations were examined. Some of the significant
observations may therefore have been due to chance. Tt
should also be noted that in these studies risks arepresented with diITerent lag intervals in tbe associations of53

doses and effects that may represent subjective decisions
based on posterior views of the data. The results should
thus be interpreted cautiously.

223. The study of workers at the Sellafield plant [S14]included 10,000 monitored workers with an average
cumulative recorded dose from external exposure of
124 mSv. The average length of follow-up was 22 years.
When exposures were lagged by 15 years out notnecessarily for other lag periods), there were significant
associations between dose and mortality fiom leukaemia@ = 0.04), cancer of the bladder @ = 0.02), multiple
myeloma @ = 0.01) and all lymphatic and haematopoietic
cancers @ = 0.03).
The study of workers at United Kingdom Atomic
224.
Energy Authority plants included 22,000 workers with aradiation record, who were followed for an average of 23
years [Fll]. The average cumulative recorded dose fromexternal exposure was 40 mSv. When exposures were
lagged by 10 yeas, there was a significant trend in
mortality with radiation dare for cancer of the uterus @ <0.05) and cancer of the prartate @ = 0.01). A case-control
study of cancer of the prostate was carried out in the
Atomic Energy Authority workforce [R25].Although therisk of prostate cancer in that study increased significantlywith increasing level of external exposure, this association
was limited to subjects who were probably contaminatedwith radionuclides.
The study of United Kingdom Atomic Weapons
Establishment workers included 9,000 employees with aradiation record, who were followed for an average of 183
years [%I. The average recorded cumulative whole-bodydose was 8 mSv. When exposures were lagged by 10 years,
there was a significant association between mortality anddose for all malignant neoplasms @ < 0.05),as well as forcancer of the lung. A sigruficant association between
radiation dose and cancer of the prostate was also obselved
among workers monitored for exposure to radionuclides.
The trend for all cancer mortality was paAcularly strong inworkers monitored for radionuclide exposure @ c 0.001)
and was mainly athiiutable to the dose-related increase mlung and prostate cancer mortality.
225.

226.
The study of workers at the Chalk River
Laboratories of Atomic Energy of Canada Ltd. in Canada[G3, H G ] covered 8,977 male workers who were monitored for external radiation and who had an average
cumulative dare of 52 mSv. The most recent publication
evaluates mortality in 19561985. When exposures were
lagged by 10 years, there was a sigrufint association @= 0.06, based on four deaths) between cumulative
radiation dose and mortality from leukaemia, excluding
chronic lymphocytic leukaemia.

227.

For the Hanford study, the internal analyses are
based on data from 33,000 monitored workers employed1994 REPORT

for six months or longer, with an average cumulative doseof 26 mSv above background. The most recent report onmortality was for the period 1945-1986 [G16]. Of the 24
specific cancer categories evaluated, only cancer of thepanaeas and Hodgkin's disease, which do not seem to be
associated with radiatior~ in other studies, showedsignificant positive correlations with radiation dose, with
one-tailed p values of 0.03 and 0.04, respectively. In
previous analyses of UIC Hanford data, multiple myeloma
was the cancer most strongly linked with radiation dose[GS]. However the findings have changed with additional
follow-up, and the one-tailed p value obtained in the mostrecent analysis was 0.10. In addition to the analyses
descnid above by Gilbert et al., the Hanford data havealso been analysed by other authors (see, for example,
P(5J). These authors have reached conclusions very
different from those of Gilbert el al., primarily owing totheir usc of non-standard and inappropriate statisticalmethods, which failed, among other thmgs, to allow
properly for age at death, calendar year of death.
occupation and length of employment. They will not,therefore, be discussed f u d ~ e here.
r

228.
The study of workers at the Rocky Flats plant(W7] included 5,000 white liiales employed for at least
two years and followed for an average of 14 years. The
average recorded cllmulative dose from extcn~alexposure
was 40 mSv. No overall association with external radiation
exposure was found.
229.
The studies of workers at Oak Ridge National
Laboratory included 8,000 white male workers hired
between 1943 and 1972. Their mean cumulative dasefrom external exposure was 17 mSv. In an initial report,nowhich included mortality to the end of 1977 [a],consistent gradients of cause-specific mortality weredetected for radiation exposure. However, in a subsequent
report, which included mortality to the end of 1984 p 2 1 ] ,a significant association was found between mortality fromall cancers combined when exposures were lagged by 10
years @ = 0.01) and 20 years @ = 0.001). It is noted thatthese results are based on non-standard statistical methods
in which, for example, a group of nien with an unusually
low mortality from cancer were included in the unexposedgroups. A further analysiq of these data [G9],using
methods similar to those applied to the Hanford data,
derived estimates of excess relative risk per sievert for all
cancer mortality similar to those given in [W21] but withmuch wider confidence intervals. The excess relative risks
were 2.9 (90% CI: 0.465) based on a lCkyear lag and 6.1
In a(90% CI: 1.5-120) based on a 20-year lag [Gg].
further analysh in h e same report [G9] it was shown thatthe significant associations were largely due to smokingrelated cancers. In addition it was shown that there weresignificant positive correlations of non-canccr mortality
with radiation dose for diseases known to be related tosmoking. It thus seems likely that confounding bysmoking may have contributed to the significant positive

correlations for cancer mortality seen in this study,
although the original authors disputed this and pointed toother complexities p 2 0 ] .
230.
Although the significant trends noted above may
represent specific hazards peculiar to those cohorts, there
is of course the danger of chance results appearing whenmany types of cancer are studied separately in many
cohorts, and overall conclusions may be strengthened if
the available data can be grouped in one or more ways.
Two partial groupings have so far been carried out The
fitst is a joint analysis of combined mortality data on
workers at three installations in the United States (theHanford site, Oak Ridge National Laboratory and the
Rocky Flats nuclear weapons plant) [G17J. The second isbased on the United Kingdom National Regisby for
Radiation Workers, which comprises workers at sites
operated by Brilish Nuclear Fuels M., the Ministry of
Defence, the United Kingdom Atomic Energy Authority,
and Nuclear Electric
Table 35 sbows estimates ofexcess relative risks with 90% confidence limits, ascalculated in these two comprehensive analyses. In the
combined analysis of data from the United States, nosignificant association was seen between radiation
exposure and all cancer or leukaemia mortality, but it wasseen for multiple myelonla @ = 0.04) [G19]. Since then~axirnumlikelihood estimate for leukaemia occurred at avalue that would have led to negative excess relative risks
for workers with the largest doses, the estimate has beenreported as negative without assigning a value. Estimates
based on a further analysis of risk estimates froni data of
the combined studies in the United Slates and of theUnited Kingdom registry have also been calculated [K21]
and are also given in Table 35. For comparison, risk
estimates based on analyses of an appropriate subsectionof the survivors of the atomic bombings in Japan are
shown as well. The studies of nuclear workers covered
only individuals exposed in adulthood, they included very
few women and the follow-up period after exposure wasshorter for nuclear workers than for survivors of theatomic bombings in Japan, so that risk estimates for theentire life span study are not directly comparable withthose based on the nuclear workers. In addition, dose.
estirnates for the workers tend to be estimates of wholebody dose and are not directly comparable with the organdose estimates in the cohort of survivors of the atomic
bombings. Another uncertainty arises from the possible
confounding by carcinogenic chenlical exposures innuclear facilities,particularly in reprocessing facilities suchas Sellafield, one of the main sources of leukaemia risk
A low-dose-rate reducZion hctor has not been included in
the figures for the life span study. For all cancers, thepoult estin~atehorn the combined workers studies is close
to the cstiniate f ~ o mthe Japanex: data, with the 90%
confidence interval extending from less than zero to about
twice the upper confidence liliiit for the Japanese data. For
leukaemia, the point estiniate from the combined workers
studies is about the same as the estimate based on them].

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCRJOGENESIS

55

Japanese data, without a lowdosc-rate reduction hctor
applied. The confidence intervals extend from less thanzero to several times the upper confidence limit 6om theJapanese data. Results from the three studies are
summarized in Table 36.

axid 0.08 Sv. The proportion of workers with an annual
dose S.25 Sv in 1949 and 1950was 507~80%
in plant A
and 35%90% in plant B.From 1%8 onwards in plant A
and 1974 onwards in plant B, the annual radiation doses
to staff did not exceed 0.05 Sv on average.

Most of the studies of workers in the nuclear
231.
industry have not been able to take account of data on
smoking habits, a serious problem if tobacco use issomehow related to radiation dose. It was possible to carryout a case-cohort study of lung cancer among white maleradiation workers at the Hanford plant in which data on
tobacco use were obtained 6om occupational medical
records [P25]. The analysis took account both of thecase-cohort design and changes over time in the quality ofthe data on tobacco use. Tobacco use was not strongly
related to the level of radiation exposure. and adjustment
for tobacco use did not greatly modify the results. With orwithout adjustment for tobacco use, the estimated risks perunit of cumulative equivalent dose were negative, and the
95% confidence intervals were wide and included values
several limes those estimated from populations at higher
doses and hlgher dose rates. A cross-sectional survey of
tobacco habits has also been carried out within theworkforce of the United Kmgdom Atomic Energy
Authority [C32]. There was little evidence for an
association between level of tobacco smoking andcumulative radiation dose.

So far, the health of more than 80% of the234.
workers who began working in these unfavourable conditions has been followed for over 40 years. During theearly years, chronic radiation sickness (defined as chronic
fatigue, depression and an altered blood pidure p30D wasconunon, and the mean total dose among affected cases
was about 3 Sv. It was subsequently determined that suchcases rarely occurred in persons wbose annual dose
remained below 0.25 Sv or whose total d w remained
below 1 Sv. The cessation of exposure or the reduction of
its intensity to levels close to those more recently regarded
as permissible limits (<0.05 Sv a-l) led to a recovery
process that resulted in the normalization of the bloodcount for 80% of the individuals affected by chronic
radiation sickness. Also, persons transferred, forprophylactic reasons, away from contact with radiation
once their total doses of gamma-radiation had reached acertain level did not subsequently develop radiation
sickness. At both plants, workers whose total external
gamma dose exceeded 1 Sv and those who received over0.25 Sv in any one year had substantially hlgher cancer
mortality than other workers Fable 37). The cancer
mortality in other workers with lower doses was shown tobe similar to that of the population as a whole.

232

It is noted that fonnal combined analyses of

updated mortality data from Sellafield, the Atomic Energy
Authority and the Atomic Weapons Establishment in the
United Kmgdorn as well as fomial combined analyses ofthe data from Canada, the United Ibgdom and the United
Slates have recently been completed; the data were not,however, available for the Committee to review at this time.
In addition, an international collaborative study of cancer
risk among nudear industry workers m 14 countries isunder way, using a common core protocol, under the
auspices of the International Agency for Resear& on Cancer[C33]. This study should result in more precise direct
estimates of cancer risk associated with lowdose-rate
external radiation exposures in the future.
233.
Information has recently become available concerning the radiation doses and mortality of workers at thereactor and reprocessing plants at the Mayak nuclear
weapons facility in the Russian Federation [ B n , B30,
N4]. In the initial period of intensive activity, during
start-up and the early years of operation, average radiation
doses to the staff were substantially higher than would
now be permissible. The avenge annual doses received byworkers in the nuclear reactor (plant A) for the years
1948-1956 are estimated to be have been 0.20,0.40,0.31,
0.18,0.15,0.20,0.09,0.10 and 0.05 Sv. From 1949-1962,
the average annual doses received by workers in the radiochemical processing plant (plant B) were 0.48,0.94,1.13,
0.66, 0.31, 0.20, 0.21, 0.16, 0.18, 0.11, 0.15, 0.15, 0.11

Individual film-badgedosimetry data are available
235.
for 3,098 men and 1,453women who startEd work at thetwo installations between 1948 and 1953 and for an
additional 1,987 men and 362 women who started work
between 1954 and 1958 P I . The average cumulative
doses for the men in these four groups vary from 0.49 to
245 Sv, and the doses for the women are also thought tobe hlgh. Data on total cancer and leukaemia mortality inmen to the end of 1989 are shown in Table 38. When
compared with national rates in the former Soviet Union
for 1970-1986, an elevated risk is apparent for all cancer
mortality in the subgroup with the highest average exposures. This effect appean to be primarily due to a large
excess of leukaemias (see Table 38). The excess relativerisk of leukaemia per gray has been calculated only for the
subgroup in which there was a sqiticantly increased risk:
it is estimated to be 1.4 G~-'.
The death rate in thissubgoup was 25 per 100,000 person-years compared with
5.5 per 100,000person-years expected from national rates.
The paper states that these results agree well with the dataon the survivors of the atomic bombings if a low-dose-rate
reduction factor of 2.7 is applied to the survivor data. In
interpreting these figures it should be noted that expectedvalues arc based on general population rates, which may
not be appropriate in this selected population In addition,
the national rates for 1970-1986 may be inappropriate foryears before 1970. The relevant data for earlier periods are

UNSCEAR 1994 REPORT

56

often not available. No data on women are available atpresent
236.
In a separate analysis [D26], mortality patterns
during a #year period have been analysed for 931
persons who worked at the fmt Soviet nuclear facility
during 1949-1953and werc exposed to radiation under themast unfavourable conditions. The average accumulated
dose from gamma-radiation was 3.26
0.13 Gy. All
individuals were subject to individual dosimetric control
and systematic medical monitoring. The total number ofdeaths during 1952-1989 was 177, of which 22.6% were
due to malignant tumours and 6.2% to Icukaemia. The
proportion of deatlis from different causes and the averageage of deaths varied over the decades. During the Erst
decade, seven persons died of leukaemia (26.9% ofdeaths), two persons of aplastic anaemia and nine ofaccidents (30.8% of deaths). During the second decade theproportion and frequency of solid tumours rose from 18%
to 23%. As would be expected in an ageing population,
the beginning of the r i a l decade saw thc relative andabsolute number of deaths from cardiovascular causes rise(the average age of death was about 60 years). Therefore,
the carcinogenic effect has been detected only for acuteleukaemia, which developed in the first 5-10 years after
the first exposure at high total doses (>3 Gy).

+

237.
In another Russian occupational study, thefrequency of lung cancer was investigated aniong 2,346
workers in the Mayak radiochemical plant who were
exposed both externally and internally to plutonium [ H l q .
External exposures were determined by film-badge dasimetry, and lung doses from inhaled plutonium were determined for all individuals using measurements of theexcretion of radionuclides in urine and a lung clearance
model. The relative biological effectiveness of plutonium
alpha particles was taken to be 16. Mortality was studied
during 197CL1989, at the end of which time the totalcollective combined dose to the lung in the group of 2,346
workers was 4,812 Sv. Of that combined dose, 3,327 SV
was from external exposure and 1,485 Sv from inhaledplutonium (RBE for alpha particles = 16) The number ofdeaths observed and the nunlber expected from national
rates in the former Soviet Union are shown in Table 39.
The risk of mortality increased with increasing equivalentdose and was significant among workers in the highest
dose group. Overall, the relative risk was 1.8 SV"
compared with 1.63 SV-' for the survivors of tbe atomic
bombings ([SA, Table 4: both sexes) The authors also
compared their estimate of the lifetime risk for lung cancer
in these workers, 0.033 SV-', using an internal control andapplying a low-dose-rate reduction factor of 2, with the
ICRP-derived value h r n the survivors of the atomic
bombings, 0.0068 SV-'. They pointed out that against
national statistics the result would be 0.014 SV-', closer tothe ICRPderived value. Even better agreement with the
ICRP value would have resulted if the low-dose-rate
reduction factor had not been applied (equivalent to a

reduction factor of 1) It should be noted that a substantial
part of the occupational exposure (about 25%) is fromplutonium alpha partides, and for these a low-dose-rate
reduction factor would not be expected to be applicable.
Also, the contribution from the alpha particle portion
depends on the value of RBE selected (16 was used). A
more co~npletestudy of these workers would include
infonnation on the smoking habits of the workers, on thepossible influence of the healthy worker effect and on the
precision of the dosimetry.
238.
Some information on the effects of low-dose-rate
exposure to external gamma-radiationon subsequent breast
cancrr risk is available Gom a study of about 1,200
wornen who worked from 1939 to 1%1 in the United
IGngdom with paint containing radium [BE,B35J The
study is fully d e s c n i in W i n III.B.2 These women
accuniulated small body contents of 226~a.
However, theyalso received external irradiation to the breast at a rate of
0.05-0.2 Gy a-l, resul ting in accumulated doses up to morethan 1 Gy (average 0.4 Gy). The breast cancer mortality
in these women to 1January 1986 was greater than in thecontrols (28 deaths compared with 205 expected) but was
not statistically significant Fable 40). The women were
subdivided into two groups, aged 4 0 and rM years at thestart of their luminizing work, and in both groups the ratioof obscrved to expected deaths among those with gammaray absorbed doses c0.2 Gy was higher than that for
women with gamma-ray absorbed doses of at least 0.2 Gy
Fable 40). For wonieri less than 30 years of age, the tinie
distribution of these deaths as a function of years of
employment shows a significant increase in excess deaths
from breast cancer only aAer 3 0 4 years of exposure.
While this timing is consistent with an effect of radiation,
the numbers arc too small to draw conclusions. No
leukaenii;~~
werc observed in this population In analysis
of dial painters from the United States, Stebbings et al.
[S42] did not fiid excess breast cancer that could be
attributed to the radiation exposure.
239.
Additional studies of radiation workers werecarried out in India, when: there are two studies: one ofworkers in the atomic energy community and theirfsrnilics in Bo~iibayIN31 arid the other in Tarapur p 2 ] .
hi both cascs Uie numbers involved are small, about 5,000
people, and the length of follow-up is short (1975-1988 in
Bombay, 1971-1988 in Tarapur). In Bombay thestandardized mortality ratios were 80 and 65 for male
employees and female family members compared tonational statistics, and there was no evidence of a radiation
effect In Tarapur the standardbid mortality ratio for
ernployecs and their families was 160 for all cancer, which
was not significantly different from 100. The standardizedmortality ratios for leukaemia were 238 for employees and222 for families, but again neither was signifant. These
Indian studies are not at this point able to make any
contribution to risk estimation, but they may provide abaseline for more cmprehcncive studies in tbe future.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

57

L Exposure to natural background radiationindoor and outdoor exposure rates. One exception is a
Chinese study, in which two neighbouring regions having

240.
External exposure of the population to natural
sources, such as cosmic rays and tel~esbialgamnia rays,varies with geographical location, and several authors haveattempted to examine the risk following low-dose-rate
exposures by comparing cancer mortality or incidence
rates in different geographical areas. Despite the obvious
attraction of having large populations available for study,
such attempts are h u g h t with difficulties. These include
uncertainties in the doses actually received by individuals.
geographic variability in the accuracy of cancer diagnases,
and confounding with the numerous otber environmental
factors that may well have a much greater influence on
cancer risk Furthermore, when geographical areas arec o m p a d , exact matching of control groups is difficult It
is not surprising, therefore, that studies that have attempted
to conelate exposure to background gamma-radiation withcancer mortality or incidence without carefully considering
these other factors have at times produced erratic andimplausible results.

different levels of exposure to background radiation(owing to the high thorium content of the monazite sandsin one of them) were selected for study [H35, W8, W15,
W16]. In both regions the wewhelming majority of the
inhabitants had lived in the area for their entire lives.
Exposures were determined by measurements not only atfixed locations indoors and outdoors but also in a sample
of individuals in each area who wore personal dosimetrrs
for two months. The average annual dose in the red bonemarrow was estimated to be 1.96 mSv in the highbackground area and 0 . n mSv in the control area. During
1970-1985 the age-adjusted mortality rates for leukaemia
in males were 3.32 and 3.82 10.' PY" in the highbackground and control areas, respectively (16 and 17
deaths), while in females the rates were 2 2 1 and3 5 6 10'5 PY" in the high background and control areas,
respectively (10 and 16 deaths), and consquently notsignificant This study thus provides no evidence for aradiation effect following low-dose protracted exposure
throughout life, since leukaemia rates were lower in the
population with higher exposure living on radioactive
monazite sands. However, the low doses and small
numbels of cases are such that the study had low statistical power to detect an excess risk, given that one existed
For example, a typical individual in the high backgroundarea would, by age 50 years, have received a red bonemarrow dose about 60 mSv greater than one living in the
low dose area. Based on estin~atesfrom the life span study
cohort Fable 8, Part XLI), doses of this magnitude would
be expeded to result in a relative risk of leukaenlia of theorder of 1.2 Relative risks of this magnitude arc very
difficult to detect epidemiologically, so even if observation
is extended over a lifetime it will be difficult to obtain adefinitive result. Similar considerations apply to many of
the smaller occupational studies, although some of theselowdose studies can be expected to pmvide an upper limit
to the risk and therefore make a useful contribution toradiation-induced cancer risk evaluation.

241.
Recent calculations have been made of the p m
portion of deaths f b n various cancers caused by natural
background radiation [D7]. These calculations used themodels of the B E E V Committee [C12] for leukaemia andfor solid turnours, which were derived h m data on thesurvivors of the atomic bombings in Japan They predictthat about 11% of deaths from lcukacniia mlght be causedby postnatal exposure to natural background sources otherthan radon, while for other fatal cancers the figure is about
4% or Iw [DA.In addition to the hlgher relative risk hleukaemia, the influence of other environmental risk factors
on subsequent leukacmia risk is less than for many othertypes of cancer risk, and the interval between exposure andany subsequent risk is generally much Iw for leuhernia
than for other types of cancer. Thus the effect of expantre
to backgmmd radiation is much more likely to be assessable for leukaemia than for most otber fatal caners.
However, studies in Conneaicut P I , Japan [I2, I l l , S.17,
France f121 the United States [H34, J3], Sweden p l ] andChina [H35,W8,W15, W16] found no significant association between leukaemia and background radiation An early
study in Scotland found a significant association W e e nnatural background radiation and leukaemia (excluding
chronic lyrnphocytic leukaemia) but concluded that even forleukaemia a proper interpretation of geographical variations
can be made only when the etTect of social and economic
facton can also be taken into account [q.
A later study
in the United Kingdom on childhood cancxrs also reported
a statistically significant effect [K7], but the statisticalmethods used wen: obscure; the mull is not only difiicult
to mtcrpre€,but it was not confimied in a subsequent report
FI131242
Few of the above studies have attempted to relate
the observed Ieukaemia rates to realistic estimates of dose,talung into account migration and differences between

243.
'Ihyroid disease was also examined in a Chinese
study of high background radiation [Wlq. Cumulative
thyroid doses at age 50 years were estimated to be about
0.14 Gy among those living in the high background areaand 0.05 Gy among those living in the control area, adifference of 0.09 Gy. Approximately 35% of theaccumulated exposure was received during childhood,which appears to be a sensitive time for thyroid
carcinogenesis Fable 8, Part XI). Physical examinations
were camed out on approxiniately 1,000 women fromeach area in the age group 50-65 years w 1 7 ] . For all
nodular thyroid disease, the relative risk for residents of
the high background area compared with that of residentsof the control area was 1.02 (95% CI: 0.76-1.39, while
for slngle nodules it was 1.13 (95% CI: 0.82-155), andthe difference, while positive, was not significant The
authors concluded that an excess thyroidal exposure

58

UNSCEAR 1994 REPORT

totalling about 0.1 Gy delivered over a lifetime, much of it
dunng the adult years of life, did not d t in a significantly
increased risk of dinically detectable thyroid tunours.
Chromosome abertation hquencies were also studied andfound to be significantly higher in the high backgroundregion than in the low background region [W17].
Where the use of different building materials
results in differences in the rates of exposure to background gamma-radiationwithin a single geographical area,
the case-control study provides an alternative method ofinvestigation. This approach has been adopted in two
studies of acute myeloid leukaemia in Sweden p,F8,
F181. In both studies the exposure to background gammaradiation was assessed using an index that took into
account the time spent indoors and outdoors and thebuilding material (stone, wood etc) in the homes andworkplaces of the subjects. In each study there was amarginally significant association between their risk of
myeloid leukaemia and exposure to higher backgroundradiation (0.04 Gy in 20 years compared to 0.02 Gy in 20
years) aRer adjusting for confounders, with relative risksof 2 2 (95% CI: 1.Cb4.9) in one study and 2 0 (95% CI:
0.9-4.3) in the other. However, the index of exposure was
crude, and in a case-control study of multiple myeloma by
the same autliors, using a similar design, significantly
fewer cases were found in the high exposure category ofbackground gamma-radiation than in controls [F17].
244.

Several geographical studies have reported an
245.
association between the amount of hllout in southwestern
Utah from nuclear tests in 1952-1958 and subsequent
leukaemia rates (see, for example, [MID. Accordingly, acase-control study with 1,177 individuals who dKd ofleukaemia and 5,330 who died of other causes (controls)
was conducted using estimates of dose to bone marrow
determined fiom fallout deposition rates and the locationof the individual's dwelling [S48]. For all leukaemias
other than chronic lymphocytic leukaemia, when all ages
and all time periods aRer exposure were combined, there
was a weak association with bone marrow dose that was
not statistically significant However. a s@cant
association was seen for those individuals who died when
they were less than 20 years old @ = 0.02) in the periodof highcst exposure, 1952-1957 (p = 0.04), and for thoseindividuals who died of acute leukaemia, especially acutelymphocytic leukaemia (p = 0.009) (see Table 41).
Subgroups combining tl~emodifying factors shown in
Table 41 werc defined before the analysis. In addition to
the results given in Table 41, a significant association withdose was found for acute lcukacrnia discovered from 1952
to 1963 among individuals who were younger than 20
years at exposure, with odds ratios of 1.33 (95% '0:
0.64-274) in the 3.CL5.9 niGy dose category and 7.82
(95% CI: 1.90-322) in the 6-30 niGy dose category. A

non-significant association with dose was also found forchronic lymphocytic leukaemia. The dose waspredominantly from external low-Ll3 radiation. No
significant associations were seen in other a priori defined
subgroups, including those in ruero during the fallout
exposure period. Tile obscwed risks in this study wereapproximately double those predicted by the estimates
based on tl~elife span study cohort, but the difference was
not statistically significant.

A series of releases and accidents occurred at the246.
Mayak nuclear weapons facility at Chelyabiik43 in thesouthern Urals. In the early 1950s, liquid wastes with a
total activity of 100 PBq (in beta emitters) weredischarged into the Twha River. As a result, the 124,000
people living along the Techa and Iset Rivers received
internal and external radiation exposures. The long-term
consequences of this exposure are being investigated in themart heavily exposed prtion of this population, consistingof 28,000 people who lived on the banks of the Techa, ofwhom about a quarter were Tartars or Bashkirs and therenlainder were Russians. Efforts have been made toreconstruct internal and external doses for this cohort
Individual extenial dose estimates are not available forcohort members; however, average external doses havebeen estimated on a village by village basis, while internal
contamination has bcen measured using a whole-bodycounter on over 12,000 individuals (D27, K261. Anotherissue of concenl is the possibility of confounding effects
from other liquid wastes containing toxic chemicals. The
cohort was defined as all people living in the defined areasurrounding the Techa River on 1 January 1950. It wasassembled in 1968 using taxation and medical records,
supplemented by lists of persons compensated during
evacuation. Data are available on the vital status of thecohort up to 1983, by which time about 8,000 people were
known to have died and 6,000 to have moved away.
Enugration is clearly a special problem as is the variable
quality of the data. Although efforls are being made to
determine vital status for all cohort members, deathcertificates are routinely available only for those deaths
occurring in the local area, so information on the cause ofdeath is available for only about two thirds of the known
deaths. Of those for whom the cause of death is known,
about 15% had cancer indicated as the underlying cause ofdeath. Special efforts have bcen made to collect data on
cases of leukaemia, and amrtainment is believed to behigh. Data on morbidity from other types of cancer has
been obtahred fmm cancer centres in the Chelyabinsk
region; these data include about 17,000 of the mostheavily exposed mcmbcrs of the cohort. Results to dateindicate an inc~easingrisk of leukaemia, especially inhigh-dose goups, and of total cancer mortality withincreasing dose (Figure XII). Analyses of data for several
cancers otl~erthan leukae~niahave shown excess risks thatare not significant [K18]. Table 42 summarizes data forseveral site-specific analyses, while Table 43 provides
more detailed data on the leukaemia dose response.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESISIn 1957 a radioactive waste storage tank at the247.
Mayak facility exploded. The explosion, called the Kyshtym
accident, contaminated a large area of the southeastern
Urals, known as the East Urals radioactive trace [K19].
Tbe resuspension of activity from a storage pond at the
Mayak facility in 1%7 resulted in small exposures in anarea largely included within the East Urals radioactive
trace. More than 270,000 people were living in the area at
the time of the 1957 accident Marrow dose estimates forthe 20,000most heavily exposed pcople are estimated tohave ranged from 0.03 to 0.25 Gy. Mortality andmorbidity in this group are being monitored. Little
information is currently available on the cohort
Since the cohorts of environmentally exposed
individuals in the southem Urals are a valuable source of
information and potentially important with respect to lowdose radiation risks, efforts should be made to inlprove thequality of the individual exposure estimates. In addition,
the lack of detailed information on data collection methods
and the incompleteness of the mortality data continue tolimit the interpretation of risk estimates derived fromcurrently available data.

248.

To investigate the effects of the accident at the249.
Chernobyl nuclear power station in 1986, a detailed study
was camed out of cancers diagnosed in the period 19811990 in residents of the three districts of Ukraine that weremost heavily contaminated with radioactive cacsium andthat had not been evacuated p341. This involved a searchof oncology, haematology and other records in theregional and district hospitals and in specialist institutes.
Annual age-specific incidence rales for leukaernia and forall other cancers, excluding thyroid cancer. are shown in
Table 44. The numbers arc small, but at ages 0-14, 15-44
and 45-64 years, the age-specific incidence rates arebroadly similar before and after 1986. At ages ~ 6 years,
5
the observed incidence of leukaemia incrreased abruptly in
1987 and in subsequent years remained two or three times
higher than the pre-accident rates, while the incidence of
all other cancers, excluding thyroid cancer, increased in
the year aRer the accident by about one third andremained at about that higher level in subsequent years.
These increases do not follow the usual pattern forradiation-induced cancers, in that they are confmed to theoldest group and, for cancers other than leukaemia,
appeared before the usual latency period. It scenls likelythat they are attributable to local concern about cancer
after the accident, which led to a lnore thorough investigation of eldcrly patienls for cancer. Before 1985, theincidence rates of leukacnlia and of all cancers combuled
werc lower at ages 265 years than in o(hcr castern
European countries. Since 1986, the rates have been morein line with those in other countries, suggesting underdiagnosis in the elderly before the accident This s w e yalso included data on thyroid cancer, and these are
discussed in Section III.A.1. It should be noted here thatthe international Chernobyl project [I31 did not End any

59evidence that the incidence of leukaemia, thyroid cancer
or other cancers had increased in the short period up tolate 1990 in people living in contaminated zones comparedto those living in uncontaminated zones in Ukraine,
Belarus or the Russian Federation. Also, cancer registrystudies to date have not linked increases in childhood
leukaemia with the Chernobyl accident [P38] although thefollow-up may not ye1 be sufficient for an effect to be
detectable [L22].

250.
The risks of low-dose-rate external exposure to
low-LET radiation are currently obtained by extrapolation
fiom high-dose-rate data. The quantitative observations
already available for workers at nuclear plants in the
United States and the United Kmgdom now provide somedirect evidence that these estimates of risk may bereasonable. The study of workers in tbe United Kingdom
shows a trend with dose for leukaemia; however, taken
together, these studies have such broad confidence
intervals that they could also be consistent with no risk atall. Firmer conclusions should be possible once theinternational ovewiews of these occupational data that areunder way have been completed. The implications of theavailable results for dose-response relationships and theeffect of protraction of exposure were discussed in the
UNSCEAR 1993 Report [Ul], Annex F, "Influence ofdose and dose rate on stochastic effects of radiation".
The current observations on Russian workers at
the Mayak plant demonstrate a carcinogenic effect of
exposures to high doses of external gamma-radiationdelivered at low dose rates and are also broadly consistent
with the results derived from the survivors of the atomic
bombings. The data are indicative of a dose response forgroups of workers with different exposure levels It is
hoped that further study of these workers and, possibly, of
additional cohorts will improve the estimates of risk fromthese potentially important data.

251.

252

The study of radioactive fillout from the Nevada
test site pravides some indication of the ability of external
doses of low-LET radiation in tbe range 6-30 mGy
delivered at low dose ratc to cause leukaemia, especiallyin persons expclred in childhood. The risks derived fromthe association scen in this study are somewhat higher
than, but consistent with, the risks derived from cxposuresdelivered at high dose ratc. The great uncertainty inestimating exposures 30 years later, however, renders any
conclusions doubtful.
The data on the populations exposed to radiation253.
as a consequence of releases into the Techa River and the
Kyshtym accident are also potentially important sources ofrisk estimates, especially for leukaemia, and of informationon the nature of risks in different ethnic groups. As with

60

UNSCEAR 1994 REPORT

the studies of the Mayak workers, the interpretation of risk
estimates in thcse populations is complicated by thepresence of both internal and external exposures as well as
by possible exposure to other carcinogenic substances that
may be highly coml;ttcd with radiation dose. The
Committee recognizes the potential importance of data on
the exposed populatiorls hi the southern Urals. It hopesthat efforts will be made to make available more information on these populations and to support improvements inthe quality of dose estimates and follow-up data, wbich
might lead to more reliable risk estimates. In themeantime, it can be said that quoted risk estimates are inbroad agreement with those derived from hlgh-dose-ratestudies.
At present there is no evidencz that external254.
low-LET radiation from the Chcrnobyl accident has
increased cancer rates in the populations living in the threemost heavily contaminated districts of the former Soviet
Union that were not evacuated P3, M211. Studies of theworkers ("liquidatorsn) engaged in the clean-up at
Chernobyl are potentially valuable for risk estimation
because the nunibers are large (several hundred thousand)and the doses appreciable (0.1-0.4 Gy or niore).

255. The study of Uiymid nodularity in wonlen mareas of high background radiation in China has provided
evidence that external exposure to low-LET backgroundradiation of about 0.1 Gy in adult life does not cause anappreciablerisk of nodular thyroid disease. Overall, studies
of cancer risk in areas of high background radiation have
yet to provide definitive infomiation on radiation effeds,
in large part because of the very lav exposures hv01\~ed
and the lack of statistical power to detea small eEfects.
These same limitations apply also to many occupationaland environmental exposures.

111. CARCINOGENIC EFFECTS OF INTERNAL RADIATION EXPOSURES

257.
Iodine-131 as sodium iodide has been used
medically in three ways. Very large amounts of *'I,
usually 2,000-5,000 MBq, have been given for thetreatment of thyroid cancer, with the aim of destroying the
thyroid gland and/or metastatic tissuc Somewhat smaller
amounts, 2OO-400MBq, have been given to treat hyperthyroidism; the resulting radiation doses are sufficient to
impair thyroid function, and the majority of patientstreated in this way eventually became hypothyroid. Muchsmaller aniounts, 0.44 MBq, have been given to diagnose
thyroid diseases. Exposure to 13'1 has also occurred as aresult of hllout following explosions of nuclear weapons,
and nuclear ir~stallatio~ishave discharged
into theatmosphere, especially during accidents.

[T13]. The most detailed study is fiom Sweden, where
second cancer risks have bcer~reported in 834 thyroid
cancer patients given 13'1. The mean total administeredamount was 4,550 MBq, and the mean observation period
was 14 years. A total of 99 new cancers developed in thepatients trcated with iodine therapy, and when comparedwith national data the standardized incidence ratio was
1.43 (95% CI: 1.17-1.75). There wcre significant increases
for cancers of the salivary glands, female genital organs,kidney and eridocrine glands other than the thyroid. Whenorgans were gmuped by estimated radiation dose, thestandardized incidence ratio was raised for organs
receiving <0.1 Gy (SIR = 157; 95% CI:1.07-221), lower
for organs receiving dmes 0.1-0.6 Gy (SIR = 1.18; 95%
CI: 0.87-156) and raised anlong organs that had received
doses of at least 1 Gy (salivary glands, stomach, small
intestine and bladder) (SIR = 259; 95% CI: 153-4.09).
The bladder and stomach reccived on average 21 Gy andthe salivary glands and small intestine 1.9 and 1.3 Gy,
rcspcctively. For the bone nianow and the breast, organ
doses wcre estimated to be between 0.1 and 0.6 Gy, andthe standardized incidence ratio for leukaemia was 2.44
(95% CI: 0.66-6.25) based on four cases, while thestandardized incidence ratio for breast cancer was 0.74
(95% CI: 0.341.40). Although some of these SIRS
appeared significant, they did not increase after 10 yeanof exposure. In addition, second cancers wcre increased inpatients riot treated with l3'l, suggesting that thc general
population may not bc an appropriate comparison group.

258.
Follow-up of patients treated for thyroid cancer
has been reported in Sweden [H31], the United Kingdom[E6]. Denmark [B24], Finland [Tll] and Connecticut

In the United Kingdom, Edmonds and Smith p]259.
followed 2.58 patients who wcre treated with an initialablation amount of 2,900 MBq of 13'1, followed, when

256.
Intenial radiatio~~exposures are of primary
importance in considering risks to the specific organs inwhich ingested or inhaled radionuclides predominantly
deposit Studies of sucli exposures include effects in the
thyroid and other organs Erom 13'1, effects in the bone andliver from isotopes of radium and thorium and effects inthe lungs from radon. Expmures from a few otherradionuclides, such as polonium, uranium and plutonium,
have been considered in niore limited studies.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

necessary, by further treatment with one or more
5,500 MBq amounts at intervals of a few month. The
mean follow-up time was just over 10 years. A total of 20
incident cancers was observed compared with 13.2
expected @ = 0 . m and there were significant excesses
for leukaemia (3 observed, 0.25 expected; p = 0.002),
breast cancer (6 observed, 253 expect4 p = 0.04) andbladder cancer (3 observed, 0.46 expeded; p = 0.01).
There were no cases of cancer of the central nervous
system. The mean dose to the bone marrow for thosedeveloping leukaemia was 3 5 Gy, while for patients withbreast and bladder cancer the mean doses to the relevantorgans were 2 1 Gy and 22.9 Gy, respectively.

260.
Some evidence of an exof leukaemia
following 13*1treatment for thyroid cancer has also been
seen in Denmark, where 2 cases of myeloid leukaemia
were found compared with 0.097 expected (0.05 > p >0.01) in a series of 194 patients, representing all patientswith thyroid cancer treated with 13'1 in Denmark between
1948 and 1972 [B24]. Record linkage studies of cancer
registry data have shown an increased incidence of
Ieukaemh following thyroid cancer in Finland, Connecticut
and Denmark [Ol, T11, T13], although treatment with
1311 exclusively was not evaluated.
261.
Several studies have been carried out of patientstreated with l3'1 for hypedyroidism. One of the mostrecent studies included about 10,500 patients treatedbetween 1950 and 1975 at seven hospitals in Sweden[Hll, H a ] The patients received a mean total amount ofapproximately 500 MBq of 13'1, and radiation dto thethyroid were between 60 and 100 Gy. Doses to organs
other than the thyroid were relatively low. An average
dose of less than 0.1 Gy was estimated for the colon,
liver, pancreas, lungs, breast, uterus, ovaries, testis, kidneys
and bone marrow. The dose to the bladder was 0.14 Gy,
to the salivary glands 0.20 Gy and to the stomach about
0.25 Gy. The follow-up was continued for a mean time of
15 years and was very complete. Cancer incidence data
were obtained born the Swedish Cancer Registry. Overall,
the number of tumours occurring one or more years after
therapy (1,543) was almost exaczly equal to the number
expected (RR = 1.06). When the data were subdivided
into 20 different sites of cancer, there were significant
increa$es of tumours of the lung (RR = 1.32; number ofcases = lB),kidney (RR = 1.39; n = 66) and parathyroid
gland (RR = 1.78; n = 30). In contrast, there was noincrease in leukaemia (RR = 0.94; 95% CI: 0.65-1.31;
n = 34), and the increase in thyroid cancer was not
significant (RR= 1.29; 95% '01: 0.762.03: n = 18).
Anlong 10-year survivors,significantly elevated risks wereseen for cancers of the stonlach (RR = 1.33; n = 58),
kidney (RR= 1.51; n = 37) and brain (RR = 1.63;
n = 30). Only the risk for stomach cancer increased overtime @ < O.M), and it tended to inmase with increasing
amount administered, although the trend was notstatistically significant.

61

The cooperative thyrotoxicosis therapy follow-up
262.
study in the United States involved evaluating patientswith hyperthyroidism for subsequent cancers. The original
study included 36,000 patients, about 19,200 of whomwere exposed to 13'1 and the radiation dose to the thyroid
was always more than 20 Gy (mean 90 Gy). They were
followed for an average of 8 years, but no increase inleukaemia or thyroid cancer was seen [D9, S2]. The
follow-up of about 1,000 of these patients (all female)
who attended the Mayo Clinic was extended to an averageof 15 years. When their mortality was compared with thatin a similar sized corltrol group of women treatedsurgically, no increase in cancer risk was observed p8].
An initial analysis of cancer incidence in the same
population reported an elevated risk of cancer (RR = 1.8;
95% CI: 1.1-3.2) of organs that concentrate 13*1(salivary
glands, digestive tract, kidney and bladder) p 9 ] , but alater report that ranked organs according to the estimateddoses received concluded that no dear patterns bad
emerged w7]. When cancer incidence in the 13'1 treatedpatients was compared directly with that in su@callytreated patients, adjusting for differences in age attreatment and duration of follow-up, relative risks were 1.0
for all maligmant neoplasms, 0.6 for leukaemia, 9.1 forcancer of the thyroid, 0.8 for cancer of the breast, 3.4 forcancer of the kidney and bladder and 0 3 for cancers of
the central nervous system. Only tbe relative risk forthyroid cancer was significantly inaeased. It is likely that
this was because the surgery group was at exceptionally
low risk much of the thyroid had been removed) and notthat the "1-treatedpatients were at an increased risk.
However, when compared with thyroid cancer incidence
rates in Connecticut, the standardized incidence ratio forthyroid cancer was 3.8 (3 cases observed compared with
0.8 expected).
263.
Follow-up has also been canied out for 1,762
hyperthyroid women who were treated at theMassachusetts General Haspital thyroid unit, many ofwhom were in the original study. These women have now
been followed for an average of 17.2 years [G7].
Comparison was based on age- and calendar-time-specificincidence rates for Connecticut white women; thestandardized incidence ratios for all malignant neoplasms
in women never treated withand in those receiving
l3'1 amounts of 4240,240-369 and >370 MBq were 1.0,
0.9,0.9 and 1.0, respectively (see Table 45). There was anexcess of brain cancer among those receiving at least
370 MBq of 13'1, but there was no consistent trend withincreasing dose. The excess reported m the initial analysisof the Mayo clinic series p 9 ] for organs that concentrate
13'1 (salivary glands, digestive tract, kidney and bladder)was not repeated in this group (SIR = 0.9; 95% CI:
0.7-1.2). AAer stratification for age and year of treatment
for hyperthyroidism, the standardized incidence ratio forwasdeveloping breast cancer for women treated with
1.9 (95% CI: 0.9-4.1) cornpared with women never treatedwith 1311.

264. The effects of the diagnostic use of 131~havebeen evaluated by Holm et al. v12,H27, H41j. A totalof 35,074 patients examined for suspected thyroid
disorders between 1951 and 1%9 in Sweden were
followed for an average of 20 years. The mean age at thetime of examination was 44 years. The average amount of
I3ll ad~ninisteredto the patients was 2 MBq, and theradiation dose to the thyroid gland was approximately
0 5 Gy, while for other organs the dose was <I0 mGy.
Record linkage with the Swedish Cancer Register
identified 3,746 caners occurring five or more years after
the initial 1311examination, and the standardized incidence
ratio for all malignant neoplasms, based on general
population rates, was 1.01 (95% CI: 0.981.04). There
were 50 cases of thyroid cancer, and the standardized
incidence ratio was initially estimated as 1.27 (95% CI:
0.94-1.67) [H12], but this was reduced to 1.18 (95% CT:
0.88-1 56) after adjustment for region of residence
There was a significant excess of thyroid cancer 5-9 years
following irradiation (SIR: 1.95, based on 23 cases; 95%
CI: 1.24-292). However, women and those o k r v e d for
10 years or more showed no evidence of an excess or ofa dose response, so it was concluded that the increaseduring years 5-9 was probably due to a high level of
medical smeillane, which led to an increased level ofdetection of indolent tumours. Furthermore, a portion ofthis early excess may have beeti related to the underlying
conditions being evaluated. Also, among 2,000 patients
less than 20 years old, no increased risk of thyroid caner
was obsewed. For the other cancers, there were significant
excesses of leukaemia (SIR: 1.34, based on 119 cases;
95% C1: 1.11-1.60), but only after 15 years, and both
chronic lymphocytic leukaemia and non-chronic lymphocytic leukae~nia showed similar significant excesses.
Endocrine tumours other than the thyroid (SIR: 1.93,
based on 130 cases; 95% CI: 1.62-229) and cancers of
the nervous system (SIR: 1.19, based on 135 cases; 95%
CI: 1.W1.41) also showed significant risks. For breast
cancer and cancers of the kidney and bladder there was noevidence of any increase (breast cancer SIR: 0.98, basedon 739 cases; 95% CI: 0.91-1.06: kidney and bladdercancers SIR: 1.08, based on 259 cases; 95% CI: 0.95-1.22).

w7].

265.
A combined anal sis of the neady 47,000
Swedish patients given '1 for thyroid cancer, forhyperthyroidism or for diagnostic purposes and includedin the studies above has also been reported. Interpretationof this analysis is complicated by differences in the
demographic charaderistics of the populations studied andthe non-ovcdapping dose ranges. Bone marrow doses were
estimated for individual patients based on total
admhistercd 13'1 activity, 24hour thyroid uptake and
ICRP tables [H26]. Standardized illcidcnce ratios for all
leukaemias, all leukaemias excluding chronic lymphocytic
leukaemia, and chronic lymphocytic leukaemia are shownby sex, absorbed d w in bone marrow, age at exposureand years after exposure in Table 46. The administrationof 1311 did not appear to influence the subsequent risk ofYleukaemia in either males or females. Nor was then:evidence for a higher risk among thosc exposed at age<40 years or in years 2-9 after exposure. The risk ofchronic lynlphocytic leukaemia, which has not been
associated with ionizing radiation, was sinlilar to that ofother types of lcukaen~ia.For the whole population (meanabsorbed bone marrow dose: 14 mGy), the standardized
incidence ratio of all leukaemia, excluding chronic
lymphocytic Icukaemia,was 1.09 (95% CI: 0.91-1.29); forthose in the 4 0 0 mGy dose group (mean marrow dose:
48 mGy) it was 1.09 (95% CI:0.91-130) and for those in
the >I00 mGy dose group (mean absorbed bone m a w
dose: 221 mGy) it was 1.04 (95% CI: 0.282.67). Thus,
although the con~binationof these three cohorts is notwithout difficulties, no clear association of cancer
induction by radiation was evident in this analysis.
266.
Several studies have been carried out of theeffects of radioiodine in fallout Over 200 inhabitants of
the Marshall Islands were exposed to a mixture ofradioiodines (l3'1, 132~,
133~,U31 and 13S~),
tellurium andgamma-radiation in Eallout &om the 1954 Bravo
thermonuclear tcst [C28, El].The whole-body garnmaray dose was estimated to be 0.11-1.9 Gy to the
Marshallcse on three atolls. The mean thyroid d m fromgamma rays and radioiodines was estinlated to be 3-52 Gy
in children and 1.6-12 Gy in adults. Many of these
individuals subsequently received anti-thyroid drugs or had
thyroid surgery. Thyroid caner appeared in 7 of 130
won~enand in 2 of 113 men over a follow-up period of
32 years. The earliest thyroid lesion appeared 9 years a k r
exposure in a girl who was 3 years of age at the time ofthe exposure. The calculated risk coeficient for thyroid
cancer was 1.4 lo4 G~-',but this estimate is uncertain forseveral reasons. The high thymid doses may have resulted
in cell-killing and decreased the number of cells at risk forcancer dcvelop~nerltFrequent thyroid surgery may have
reduced the tissue at risk, and prophylactic thyroid
hormor\e medication might have influenced the risk.
Furlhennore, tile effects of gamma-ray exposum could
not be dktinguished from thase of internal radioiodines.
The dose to the thyroid fiom the short-lived and moreenergetic radioiodines was 2-3 times greater than that froml3'1, and thus the contribution of 13'1 to the developmentof thyroid cancer muld not be determined.
267.
The pcssibility of thyroid effects in people
exposed to radioiodine releases during and after the
Chernobyl accident has received much attention. In theinternational Cbernobyl project [U],neady 600 children
aged 5 and 10 ycars Gonl contaminated and control areas
in 1990. The children had been between
were exa~t~incd
1 and G years old at the time of the accident The
proportion of children having thyroid nodules was thesame in the exposed and unexposed children
1. Morerecently, however, an increase of thyroid cancer inchildren living in areas contaminated by radionudide
deposition from the accident, where doses fiom short-lived

w1

ANNEX A: EPIDEMIOLOGICAL STUD1IES OF RADIATlON CARCINOGENESIS

mdioiodines may have been substantial, has been reported
from the Ukraine [P34] and Belarus p ] but not fromthe Russian Federation. In Belarus an increase wasobserved in children only four years after the accident In
all other studies of thyroid cancer an increased risk has
never been seen until more than five years aRer radiation
exposure [%I]. No information on the individual thyroid
doses reccived by these children is available. It is not yet
possible to determine whether the reported increases are
truly associated with radiation exposure or whether they
are a m u l t of increased surveillance for thyroid disease,which is known to result in apparent increases IBIS, B42,
C5,R11, S63, SM].

268.
A survey of thyroid disease among children in
Utah and Nevada exposed to fallout radiation from
weapons testing in the 1950s and control groi~psliving in
Utall arid Arizona has found no significant differences theincidence of any type of thyroid disease [R12]. No casesof thyroid carcinoma were found in 1,378 children thought
to have been exposed, while two cases occurred among
3,443 children who were not living in the primary fallout
area during infancy. In a recent aper, Kedxr et al. F l ]report an association between '1 exposure and thyroid
neoplasms among a cohort of about 2,500 children
exposed to fallout from nuclear weapons tests in Utah. A
total of 19 cases were observed arid about 13 expectedduring 20 years of follow-up (1%5-1986). The average
thyroid dose, based on individual dose estimates, was0.17 Gy. The estimated excess relative risk per g a y was
about 7. When the analysis was limited to the eight
thyroid cancers included in this series, the point estimateof the excess relative risk per gray was slightly greaterthan that for all neoplasms but was not statisticallysignificant (p = 0.10). As indicated by tbe authors, factors
related to the study design might have led to biases in thisestimate. These included issues related to selection anddietary recall used in the dose reconstruction. The authors
concluded that such effects were unlikely to have had alarge impact on their fmding. While this estimate is notout of line with risks seen in children exposed to external
low-LET rddiation, it is substantially higher than risks seen
in other studit.. of populations exposed to 13'1. In
particular, the risks derived in the Kerber study [Kl] aremuch larger than thase seen in the Swedish study [HI21 ofpatients, primarily adults, who had received an average
dose of 0 5 Gy for whom the (non-significant) estimatedexcess relative risk per gray was 0.4. Based on only twocases among children in the Swedish study, the nonsignificant estimated excess relative risk per grdy was 1.4.

P

Tile incidence of thyroid cancer has also been269.
studied in Cumbria, United Kingdom, near tile Sellafield
nuclear site, which has discharged both lZ9l and l3'I into
the sea and atmos here since the early 1960s [B25].
P
Measurements of '-4 were made on 130 thyroid glands
taken opportunistically at netrropsy h m adults who diedof various causes in Cumbria between Noveniber 1984

63

and September 1987. Lcvels of activity decreased with the
distance of the patients' homes from Sellafield@ < 0.001). In contrast, age-standardiiA thyroid cancer
regisbation rates for the 288 parishes in Cumbria in
1969-1986 showed a positive correlation with distancehom Sellafield (p < 0.001), witb the higher incidence atgreater distances. It was estimated that most of the sample
population received less than 0.67 j&v a-I from 124, andnone were likely to have received more than an additional
15$31a-l. Bccause of its short half-life,
could notbe measured in the sampled thyroid glands, but the authors
estimated that total cumulative doses bom the two
radionuclides were probably about equal. Such small
exposures would not be expected to result in detectableeffects of any kind, and indeed none were found.
270.
Coniparisons between the carcinogenic pote~itialin the thyroid of external radiation and radioiodines suchas l3'1 have Gequently been attempted. In view of thescant and uncertain data on increases in cancer risk
following exposure to 13'1 oudined above, suchcomparisons are difficult [C12]. Tbe National Council for
Radiation Protection and Measurements INS] found that,based on human experience, the relative effectiveness of
13'1 compared with external radiation is between zero andone half; data liom animals suggest a value between one
tenth and one. A value of one third was recommended in
the NCRP report. Shore [%I], in a more comprehensive
and recent review of the human data, found only 8.3
observed excess cancer cases from all l3'I studies
combined compared with 37.0 cases expected based onrisk estimates for external exposure. The ratio, 0.224, isabout one quarter. Evidently the protracted dose to thethyroid that results from 13'1 exposure is one reason forthis difference, but the distriiution of *'I in the thyroid
gland and the resulting non-uniformity of dose may be
another [S68].

2.

Other radionuclides

Phosphorus-32 is a high-energy beta emitter that271.
tends to concentrate in the skeleton. Repeated injections of
3 2 have~commonly been used to treat polycythemia Vera,a disease characterizxd principally by the overproductionof red blood cells. In a study of patients withpolycythcniia Vera diagnosed in 1937-1953 in the UnitedStates and followed to the end of 1961, the cumulative
incidence of leukac~niaby 15 years after diagnosis was
20% in the 32~-trcated group but only 2% in the
non-irradiated polycythemia Vera patients who had beentreated with phlebotomy, sometimes in combination withchemotherapy w34]. Detailed dosimetry calculationshave
not been perfoniied, but crude dosimetry suggests that the
average skeletal dose to these patients was about 3 Gy,
which appears to have resulted in an e x a x cumulative
incidence of leukaeniia of 18%. This risk is highcompared to that seen in patients exposed to extcrnal

1994 REPORT
low-LET radiation. In a randomized, controlled trial,
patients treated with 3% also appeared at high risk: 6% (9out of 156) patients treated with 3 2 developed~
leukaemia
compared witb only 1%(1 out of 134) htated by p h l e btomy [B33]. Extrapolation from these data to other situations may not be justifiable, however, as patients withpolycythcmia vera may be unusually susceptible to radiation-induced leukaemia owing to the nature of their underlying disease.

272
Sulphur-35is a low-energy beta emitter. Treatmentof chondrosarcorna and chordoma with Y~ injected assulphate caused severe marrow damage, as expected, but
it may also have caused the three leukaemia cases that
occurred in the nine subjerts who suwived at least twoyears
M371. It is possible that the marrow damage
would have materially increased the risk of radiationinduced leukaernia.

w1,

273.
As part of a study of iron metabolism inpregnancy, the effects of oral administration of 5 9 ~ e(abcta-gamma emitter) wcre examined in 679 pregnant
women; 705 control women chosen from the same clinicalpopulation did not receive '%e p25]. Frequency and typeof malignancy in the next two decades did not d a e r forthe two groups of women. Among the 634 exposedchildren of these women, one case of leukaemia and twocases of sarcoma were discovered, while no malignancies
occurred in the 655 children in the comparison group,
rcprcsenting a small but statistically significant increase@ = 0.03). Among those exposed, the fetal doses wcre
estimated to be 0.05-0.15 Gy.
River water heavily contaniinated with fission
274.
products bum fuel processing caused large body burdensof %r in people living along the upper reaches of the
Techa River in the southern Urals, who were using thewater for dnnkmg and irrigation. Tooth and wholc-bodycounting based on Bremsstrahlung yielded cumulative
bone marrow doses of up to 3 Gy PM].Dose contributions Gom other radionuclides wcre sniall, but external
dose rates near the river banks wcre considerable (up to
1 mGy h-I). In a cohort of the 28,000 persons mostheavily exposed, an excess risk for leukaemia wasreported (see paragraph 246).

3. Global falbut
Estimates of the average a~uiualabsorbed doses
275.
in the bone marrow Gom low- and high-LET radiation
rcccived from various sources by children born in Thurso
near the D o u ~ e a ynuclear installation in northern Scotland
have been published by the National Radiological Protcction Board [D8]. For botii low- and hlgh-LET radiation
the annual dose from fallout from atmospheric nuclear
weapons tests peaked sharply in about 1%4. For l o w - J J 3
radiation the maximum annual dose in the bone marrow

was estimated to be 650,&y, mostly from 13'cs andm ~ r while,
for higb-LET radiation the maximum annual
dose in the northern hemisphere was estimated to be much
lower, 2 6 f l y , niostly from ''%butIwith some P 8 ~ u
V O ] . The dose from strontium would have been entirelyinternal from beta radiation, while for cacsium about two
thirds of the dose would have been internal from a mixture of beta and gamma-radiation The temporal pattern of
fsllout throughout northwest Europe was similar to that
estimated for Dounreay: doses from hgb-LET radiation
were similar but doses from low-LET radiation varied
depending on rainfall. In the Nordic countries thelow-LET radiation doses were likely to have been about
twice those experienced in Britain. If doses of thismagnitude of either high- or low-LET radiation cause anappreciable childhood leukaemia risk, the incidence ofleukaemia in northwest Europe should have increased atabout the same tinie in all affected countries. Data fromthe Nordic co~lntricshave been presented [D2]. Surprisingly, in view of the small doses involved, a small but
statistically significant increase in the relative risk ofleukaemia was noted in children m the period following
the highest fallout as compared witb the preceding andfollowing periods of more moderate fillout.

4. Summary
The data summarized above provide a substantial
276.
amount of infomiation about the effects of 1 3 1on~ the riskof thyroid cancer for a very wide range of doses, from thevery high doses delivered in the treatment of hyperthyroidism to the low doses received by persons exposed
to diagnostic procedures or to radiation h m fallout The
infomiation relates mainly to individuals exposed in adultlife, and it provides little evidence that exposure to I3l1 is
associated with an increased risk of thyroid cancer,
although in some cases the follow-up periods have been
comparatively short Sigruficant excesses, all of whichmust be qualified, were reported in four studies, one ofthem in children. This lack of a clcar effect (when such
effects arc well known to follow external radiation
exposure of the thyroid) may be due to the lesser
effectivcncss of I3lI because of dase promaion andinhomogeneous distribution of the beta emittcr in the
thyroid gland. Thyroid cancer risks are dependent on age
at exposure. The risks of childhood exposure to 1311 are,however, lcss well known than those of adult exposure, so
iurther studies of children are needed.
Comparisons of the carcinogenic effectiveness in277.
the thyroid of 13'1 with that of external radiation are
difficult. Gross estimates from human experience, s u p
ported in part by animal studies, suggest that 1 3 1 ~is about
one fiftll to one Uiird as effective as external radiation.
While there have been excesses of cancer of sites
278.
other than the thyroid in cohorts exposed to high levels ofANNM A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

l3'1, the findings have not been consistent or reproducible
and may well bc due to chance. A large study in the
United States ofpatients with hyperthyroidism did not findany difference in the risk of leukaemia in patients
receiving U 1 therapy~
and in those treated surgically. An
extensive study of leukaemia in Swedish patients given
U 1 in~ adult life indicated that the administration of l3'1
did not influence the subsequent risk of leukaemia. Doses
were generally low, but even at bone marrow doses>I00 mGy no increased risk of leukaemia was observed.

279. Few studies have as yet bccn carried out of theeffects of internal exposurcs to low-LET radiation fromradionuclides of iodine other than 13'1, especially shortlived radioiodines. Such studies could provide valuable
inionnation on the effects of mixtures of radioiodines
released to the environmen4 and the Committee
recommends that exposed populations should be identified
and studied.

R HIGH-IAET RhnL4mON EXPOSURES
o m THANRADON
The risk of cancer resulting tlom the exposure of280.
human beings to hlgh-LET radiation must be establishedeither by studying the direct effects of such radiation inhumans or by knowing, as has been outlined earlier in thisAnnex, the risk of cancer for low-LET radiation andestablishmg the relative biological effectiveness (RBE) of
high-LET compared with low-LET radiation in a variety
of other biological systcnls. There are few didmeasurements of the ability of external high-LET radiation
to induce cancer in human beings. Neutron exposures at
Hiroshima (and Nagasaki) are largely ovewhelrncd by theeffects of gamma rays, as assessed in DS86 [R22], andtheir impact may not be large in terms of possible
adjustments (paragaptls 156-158). This makes it
i m p i b l e to derive either an RBE or separate risk
estimates for neutron-induced cancers from these studies.
The only distinct human data on the cffecis of neutrons
come from two criticality accidents in which the neutron
doses exceeded the gamma-ray doses substantially. TWOof the seven long-term survivors died from acute myeloid
leukaemia 19 and 33 years later. aner neutron doses of
0.12 Gy and 0.08 Gy. respectively p36]. Gamma doses
were only 0.04 Gy and 0.001 Gy, respectively. It is
diacult to construct a useful risk estimate Gom such asmall sample.
281.
In the absence of human information, manystudies comparing high-LET radiation with low-LET
radiation have b a n undertaken in a wide variety of
biological systems [14, N7, S67] to dctcrmine the relative
biological effectiveness, These have allowed thc calculation of values of quality factors or radiation weighting
fsctors for high-LET radiation p10) (see Table 47). The

65

application of these factors to derive appropriate high-LET
equivalent doses (in sievcrt) enables the risks for low-LET
radiation to be applied to high-LET radiation. End-points
involving tumour induction, life-shortening and cell hansformation are of special relevance, particularly if the RBEs
are determined at low doses of both the high-LET and the
low-LET radiation, where responses are linear and a maximum value of the RBE, namely MEM, results p4: N7,
S67]. Throughout this Section, absorbed doses of hlghLET radiation are quotcd in gray wherever possible.
Equivalent doses are obtained by applying the radiation
weighting factors (wR)of Table 47.
There is one type of hlgh-LET radiation to which282
human beings have been widely exposed internally. Thisis alpha-particle radiation, mainly from naturally occurring
radionuclides. The large body of data on the exposure ofhuman beings to alpha particles from radon and its progeny are discussed in Section LII.C.Additional informationon the effeds of alpha particles in human beings comesmainly from studies of patients either treated with 24Ra
or injected with the diagnostic contrast agent Thorotrasq
Erom studies of occupational exposure to 226Ra, 28Ra,
plutonium, or uranium dust and, to a very small extent,
from studies of radium in the natural environment Reviews have beer1 carried out by Mays [M4], the BED3 IV
Committee [C6]and Taylor et al. [TI].
It is necessary to examine this material to see to283.
what extent an excess of cancer induction has been
obscrved and whether there are any unusual features of its
induction compared with induction by law-LET radiation.
More importantly, if both the number of excess cancers
per unit population and the dose causing them issufficiently well known, a direct measure of risk may bederived for the specific organ or organs in which the
majority of the alphaemitting material becomes lodged.
As will be seen below, this is possible for both bone andliver cancer; indeed, present knowledge of risk in these
two organs derives primarily or exclusively fromexposures to hi&-LET radiation from which or withwhich low-LET risks are inferred or comparcd.

334.
After the Second World War, about 2,000
children and adults in the Federal Republic of Germany
were trcated for tuberculosis, ankylcsing spondylitis orother diseases with repeated intravenous injections of?74Ra as radium chloride w3, S39, S40J Bone is theprincipal repository for rndium that is incorporated into
the body, but as 2-4Ra has a half-life of 3.6 days, almost
all the radiation dose is delivered to the bone surface,
before the radium can be incorporated throughout the bonevolume. In beagle dogs, injected 2 2 4 ~hasa been found todeliver an appreciable alpha-particle dose to the kidneys,
liver and eyes as well [L13].

66

UNSCEAR 1994 REPORT

It was not possible to follow the entire group of
2,000 patients, but a subgroup of about 900 patients wasstudied bum 1952 onwards. Until 1988,by which time
58% of the patients were known to have died, the average
length of follow-up was 24 years (range 0-43 years) w4,
M7, MI]. The average injected amount of ZL4Rawas
0.67 MBq kg-', leading to an estimated average skeletaldose of just over 4 Gy [S40].Those less than 20 years d d
at first injection receivcd on average nearly twice theinjected amount per kilogram as those who were at least
20 years old at first injection, and because of the cnhanced
uptake of radium by gowing bone, their estimated average
endosteal dose was nearly five times that of adults(10.6 Gy compared with 21 Gy). The injections were
given over periods ranging from 1 to 45 months, withaverage values of 55 months for adults and 10.9 months
for children and juveniles

285.

286.

The most notable feature of the subsequent healthof thcse patien& is that 54 developed a total of 56 primarybone sarcomas, mostly osteosarcomas p4,5311. Cancer
incidence rates give an expected number of only 0.2, andthere is no evidence that this would have been incrcasedby the disease for which patients were being treated, as
neither ankylosing spondylitis nor tuberculosis isassociated with an increased incidence of bone cancer in
non-irradiated patients. Thus all, or nearly all, evenallowing for some possible misdiagnoses, of these bonesarcomas are likely to have been radiation-induced.

287.

The first bone sarcoma appeared only 35 years
after injection, the peak frequency was after 6-8yeaa, andthe most recent sarcoma appeared after 33 years, with theteniporal pattern of expression being similar for those first
irradiated in childhood and as adulk wS]. Only one newtumour appeared in the most recent 10 years of follow-up(i.e. 30-40 years after treatment), and it seems likely that
most, if not all, of the radiation-induced bone sarcomas
have already appeared, so that the temporal distribution isunlikely to be altered much in the future. The exress
absolute risks per gray appear to be roughly equal among
men and women, among those irradiated for tuberculosis
and spondylitis and among those who were irradiated atless than and more than 20 years of age p7J.However,
the estimated risks are not conclusive, as they depend on
the estimated individual skeletal doses, which are not very
accurate.

288.
Initial examination of the dose-response
relationship indicated that a simple linear model did not fit
the data very well and that it might be necessary toe
was also
include a quadratic tcnn [C4]. S o r ~ ~evidence
noted of a tendency towards an increased risk per graywhen the injection span was incrcased, causing the periodof irradiation to be protracted PI.A recent reanalysis of
the data has examined the dose-response relationship andalso taken into account the varying exposure periods of theindividual patients [C17]. This analysis confirmed theincreased risk per gray when the injection span wasincrcascd @ < 0.01). This might be due to an inverse
dose-rate effect (a dose-nte effect is called inverse if
instead of producing a greater effed per unit dose at
higher dose rate it produces a lesser effect), in which, forexample, an inmased injection span would allow morecell division between successive injections, thus
maintaining the number of cells at risk in the endosteum
at a hlgher level during the course of injections p26]. It
can also be explained by cell-killing, which reduces theslope at higher doses p261. The lowest average skeletaldose that was followed by the development of a bonesarcoma was 0.90 Gy, but the analysis suggested that fora constant exposure time the data were consistent with alinear no-threshold dose response. The apparent linearquadratic dcpcndence that had earlier been inferred was,in fact, the combined result of a linear relationshipbetween bone sarcoma incidence and dose for constant
exposure time and of an increase in the incidence withlonger exposurc times for constant dose. The model ofchoice was of the following form:

where R@,t) is the cumulative incidence of bone sarcoma
following an average skeletal dosc D, in gray, delivered
over a period of t months. There was no indication thatthe dependence on delivery period applied only to thelarger doses.
289.
It is possible to derivc a lifetime risk estimate forthe induction of bone cancer by alpha particles from thesestudies with 224Ra. In the report of the BEIR IV
Committee ([C6],page 208) juveniles and adults were
lrcated as slightly different in sensitivity and as risk
estimates for bone sarcomas of 188 104 G ~ for- juveniles~
arid 133 lo4 G ~ - for' adults were derived (it is noted that
if dose protraction were takcn into account, the difference
between jwcnilcs and adults would disappear, inagreement with Mays et al. w71). The weighted average
yields an absolute risk coefficient of about 150 lo4 G~-',and for fatal cancer (lethality 0.70 p101) it is about 100
lo4 G~-'.Thus the low-LEI' risk derivable for a wR of
20 is 5 lo4 G ~ - ' and, it applics to low dose and low dose
rate. It should be noted that these values are derived fromhigh-dose information and require extrapolation from highdosc to low dose and from high-LET to low-LET. It is for
thcse circu~~islar~cesthat the wR of 20 is presumed toapply. Stated lriorc generally, for radiation of high-LET
and low-LET, the lifetime risk of fatal bone cancer is
5 lo4 SV-'. This is in very good agreement with the lowL J 3 value of 0.2 lo4 SV" annual risk rate (Table 8,
Par1 VI) for a 25-year period at risk

In addition to an incrcase in bone sarcomas, there
have also been statistically significant increases in breast
cancer in these patients (14 cases observed, 4.1-6.1
expected; p < 0.005), liver cancer (6 o k r v e d , 1.1-1.2
wpected; p < 0.002) and leukaemb (6 observed, 2 e
x-

290.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

p < 0.05) and a non-slprufjcant increase in kidney cancer(5 obsetved, 24-26 expected; p c 0.13) [S41]. The
expected values were based on data from cancer registries
in Hamburg and the former German Democratic Republic[S41]. The calculated organ dares averaged 2 4 Gy for thekidney and 1.4 Gy for the liver, but doses for the brcast orbone marrow have not been published. The increase ofleukaemia has been attributed to the frequent use ofphenylbutazone by the patients with ankylosing spondylitis, but the evidencz that this drug is leukaemogenic is
weak [F14,16]. In contrast to finding from studies of theeffects of z6Ra, no carcinomas of the paranasal sinuses or
mastoid air cells have been observed p 7 ] .
It was shown by Spiess thatz4& was ineffeaive291.
in the treatment of bone tuberculosis [M3). For ankylosing
spondylitis, however, there was acceptable evidence of its
therapeutic value. The original highdose treatment was
discontinued after about 1950, but treatment involving
much lower amounts of z4Ra continued to be used. Inorder to monitor the r a n t ='Ra therapy for ankylosing
spondylitis, Wick et al. [W4, W5, W18] identified about
1,500 adult patients treated mainly between 1948 and1975. The majority of the patients had received a single
series of 10 weekly injections, each of 1 MBq ofalthough some patients received more than one series, andfor all the patients the resulting mean endosteal dose wasestimated to be 0.65 Gy. The injection span averaged
about 12 weeks. By 1988, the date of the most recent
published results, the average length of follow-up was 17
years. By that time only one patient had developed adefinite bone turnour: a fibmarcoma of the ileosacral joint
appearing 11 years after an avenge skeletal dose of
0.67 Gy. Wick et al. [W5, W18] referred to three tumours,
but two were not bone tumours in the conventional sense.
One was a rcticulosarcoma of the bone marrow and might
be more properly described as a lyn~phoma;the other wasa multiple myeloma. The number of spontaneous bonetumours expected horn national rates is about 0 5 , and theprediaed number of radiation-induced h e sarcomas
based on the Spiess series is 6. Thus, there is someevidence that for a given injection span the m~llulativcrisk
per gray may be lower for this group than for patientstreated with the original high-dose therapy. As mentioned
above, one patient in this group also developed multiple
myeloma, and six patients developed leukaemia. However,expected numbers have not yet bcen published. No carcinomas of the paranasal sinuses or mastoid air cells are
known to have occurred so far [WS].

2. Radium-226 and mdium-228
Populations exposed to skeletal alpha radiation292&om internally deposited long-lived isotopes of radium
have also been studied p26, E8, R61. Tbe best known
group comprises over 4,000 dial painters, radium chemists
and patients given z6Ra or 228Ra therapeutically in the67

United States before 1950. Treatment with intcmallydeposited radium isdopes has been discontinued. Some ofthese individuals were internally contaminated with pure
226Ra and others with various mixtures of z6Ra andz8Ra. Both isotopes have long half-lives (z6Ra: 1,600
years; 228Ra: 5.77 years). Some 87 bone sarcomas are
known to have occurred in 85 persons among the 4,775
persons "for whom there has been at least one determination of vital status" [C6]. Among the 2,403 subjects forwhom there is an estimate of skeletal dose, 66 sarcomas
occurred in 64 subjects (fewer than 2 would be expectedfiom national rates). In addition, some 35 carcinomas ofthe paranasal sinuses and mastoid air cells are known tohave occurred in 31 people for whom estimates of skeletaldose were made [C6) In unirradiated populations thesetumours are exceptionally rare. The sinus and mastoid air
cell carcinomas seem to have been caused mainly by
2 2 2 ~ gasn and its progeny. Radon-222, produced by the
decay of z 6 ~ a ,escapes fiom bone and collects in thefrontal sinuses and mastoid air cells.
Cancer mortality has also been studied in about
293.
1,200 women who worked in the United Kingdom withpaint containing radium from 1939 to 1961, whose
average level of contamination was m~ less than that of
the United States g o u p and who received much lower
doses p2,B26, B35]. By the end of 1985, one fatal bonesarcoma had occurred, compared with an expected numberof 0.17, and there had been no deaths h ~ headn sinuscarcinoma. The z6Ra content of 470 luminizers wasmeasured about 20 years after thcy had entercd theindustry. Forty-five had more than 0.05 pg, 20 had more
&an 0.1 & (the greatest being 0.6 pg), and 264 had lesshan 0.01 pg. No person who had luminized after 1941
had more than 0.05 pg. Like the United States dial
painters, each woman was also irradiated externally by
gamma rays emitted from the container of radioactive
paint that stood beside her as she worked.

In the group in the United States, there is little
294.
evidence to suggest that age at exposure influenced
ostcosarconla risk [P29]. The first bone sarcoma wasdiagnosed five years after exposure, and the fmt tunlours
started to appear at about the same time after exposure had
begun, regardless of the level of exposure
Figure Xm). O w i to the protracted exposure from@alf-life: 1,600 years), tumours have continued to appear.
Thus, in contrast to the patients treated with 224Ra.where
the risk appears to be minimal more than about 30 years
after exposurc, tumours have continued to appear morethan 60 years after first exposure. Analyses have not yet
been carried out to learn whether the rate of occurrence of
lumours per person-year at risk is increasing withincreasing time since f i t exposure, remaining constant ordemasing. For head sinus carcinomas, the first tutnour
appeared nearly 20 years after fmt exposure. and tumours
have continued to appear until 60 years after first
exposure. By 1967 no bone sarcomas or head sinusA;1994 REPORT

carcinomas had occurred in the patients in the UnitedStates who had an estimatcd average skeletal dose lessthan 12 Gy, and it was suggested that a practical threshold
might exist However, this now seems unlikely, as s i n ethen three head sinus carcinomas have occurrcd inindividuals with estimated doses of 11.8, 7.1 and 1.2 Gy,
while bone sarcomas have occurred in patients withestimated doses of 8.9 and 4.6 Gy. In addition, a bonesarcoma occurred in a British dial painter with anestimated skeletal dose of 0.85 Gy 21. In all six cases..R'
There are about
the majority of the dose was from
300 dial painters in the United States and United Kingdom
with measured average skeletal doses between 0.8 and
12 Gy,and by this time about 0.2 naturally occurring bonesarcomas or head sinus carcinomas would be expected tohave occurred among them. Thus it is likely that most or
all of these six cancers can be a s c n i to radiation [M4],and any practical threshold, if it exists at all, cannot begreater than about 1 Gy. No other bone sarcomas occurredin the United Kingdom dial painters.
295.
Rowland et al. [R6, R7] studied dose-response
relationships in the Uruted States series. An equation of
the form I = (a + $A?) exp(-yA) was found to provide an
acceptable fit to the osteosarcoma data. I, the incidence
rate, is the observed number of bone sarcomas perperson-year at risk and A is the activity of radium entering
the blood during the exposure period. In contrast, a linear
form, I = a + &4, fitted the head carcinoma data.
Marshall et al. p 3 8 , M39] developed an elaborate
twc-target model, proposing that two successive initiating
events and, later, a promoting event are required forosteosarcoma induction. The initiation events remove theability of a cell to stop dividing; the promotion went is asignal to divide associated with natural remodelling ofbone. The model also allowed for the competitive effectsof cell-killing.A third model was that developed by Raabeet al. [R20], which used time to death and average skeletaldose as the parameters and is relevant to the question ofa practical threshold (see also [C6J).All these analyses
should, however, be interpreted with caution: the intake ofradium was estimated many years after the event and may
be inaccu~ate; the distrii~ution of radium in bone isprobably non-uniform, and hot spots capable of extensivecell-killing may have occurrcd; the dose responsible fortumour induction cannot be distinguished Gom any d o ereceived after initiation; the relative mntribution of thealpha-particle emissions camlot be separated Gom theother radiations accompanying radium decay; and thehction of the total dose received by the endosteal cells
cannot be specified precisely [BME296.
In the United Gigdorn study of the dial paintels,
there was an elevated risk of niortality from breast cancer
that was not statistically significant except at one timeafter exposure p26]. However, this risk is more likely due
to external irradiation by gamma rays than to internallydeposited T6Ra (Section 1I.B.1) [B35, B361. In the dial

painters in the United States, mortality from breast canmr
was increased when compared with national rates, but theexcess was not significant wl~cncompared with local rates
15421. There was also an excess of multiple myeloma in
the United States study (6 deaths observed, 215 expeded;
p = 0.045 [S42]), but it correlated with duration of
employment (a surrogate for gamma-ray exposure) rather
than body content of radium. Fatal brain tumours andother turnours of the central nervous system in the UnitedStates series, recently reviewed, were not found to be inexcess [SSO]. Leukaemia may have occurred in earlycases, which were characterized by very high radium
burdens fC6, MU, P181, but the inadequate diagnosis andclassification of leukaemia in the 1920s and 1930s
prevents any detailed conclusion. A review of leukaemia
incidence in the dial painters in the United States found 1 0
cases of diagnosed leukaeniia compared with 9.24
expected on the basis of rates in the general population[SlS]. No leukaemia was reported in the British dial
painters exposed to relatively low levels of z6Ra, whoaveraged 37 years at risk, compared to their natural
expectation of 1.93 leukaeniia cases [B35]. Thus, except
perhaps in individuals with very high body burdens, it isconcluded that 226Ra and 228Ra deposition in the skeleton
Gom dial painting does not result in a risk of leukaemia.
297.
Three studies of the geographical association
between the level of 226Ra in groundwater or drinlung
water and cancer incidence or mortality have beenreported. The first study examined mortality between 1950
and 1%2 among almost 908,000 residents of 111
communities in Iowa and Illinois whose water supplies
contained at least 0.1 Bq 1-I (P191. Those exposed to lnore
than 0.1 Bq l1 had a death rate Gom bone c a n e r of
1.41 lo-' per year, not significantly higher than the rate incontrol cities (<0.04 Bq I-') of 1.14 lo-' per year
@ = 0.08). The second study examined nearly 64,000
residents of 28 towns where water was obtained solely
from deep wells [B3]. The water supplies were divided
into three groups by radium level. Only for bladder cancer
in males was the hlgbest
level associated with armcer rate higher than that observed for the residents of
The third
towns in Iowa with surface water supplies [a].
study examined the association between leukaeniia andP6Ra in groundwater in Florida [L14].'lheand
2 2 8 ~coiltentsaof 50 private wells in 27 selected counties
were measured. In 17 counties classed as high-expure
counties, leukaemia rates were grcater than in the 10
counties classed a s low-exposure counties. An association
with increasing levels of radium mncenbation was
suggested. A later study carried out over a longer time
also found an apparent excess of leukaemia in thesecounties 1021.
298.
The fmdings of these three studies are notconvincing and, in fact, are typical of geographicalcorrelation studies. The exposure levels were not very
different and were not based on individual e x p u r eA N W A: EPIDEMIOLOGICAL STUDIIES OF RADIATION CARCINOGENESIS

measurements. In one study there is an indication of asignificant association, but the effect noted is not inagreement with the results of the occupational studies ofhigher levels of 226Ra. It is noteworthy that none of thegeographic studies found excesses of bone sarcoma,suggesting that the positive findings for other cancers may
only be a consequence of the large number of cornand of chance, as indicated in paragraph 31. Further
studies of the effects of low-level exposure to radium
based on individual measurements might be useful. Except
for the bone sarcomas and head sinus carcinomas, no
excess of leukaemia nor of any other type of cancer ispresently ascribed to the internal deposition of long-lived
radium isotopes.

3. Thorium
Thorotrast, a 25% colloidal solution of thorium
299.
dioxide, was a commercially prepared contrast agent usedin medical radiography. It was used in several countries
tiom about 1930 until after the Second World War.
Usually given by intravascular injection it was used
extensively for the radiological diagnosis of war injuries ofservicemen in the Federal Republic of Germany and Japanand for cerebral angiography, although it was also used forother puqmes and administered by other routes.
Thorotrast is retained in the body more or less300.
indefinitely, since the excretion rate is very l o w g l ] . andRa), arealthough some of its decay products (e.g.
normally mobile within the body they have diEculty indiffusing out of the deposib of Tho2 in which they areaeated. The colloidal material injected rapidly becomes
granular, and Thorotrast granules are taken up by
phagocytic cells anywhere in the body, allowing transport
to other sites such as lymph nodes. Alpha irradiation
around phagocytes containing Tho2 granules, as in theliver, is localized to aggregates assumed, for dosimetricpurposes, to be of spherical shape and to have a radius up
to 100pn. The average organ dose cannot be easily
specified because of self-absorption of alpha particles in
the aggregates. It depends, among other things, on theanlount of Thorotrast injected but is not proportional to it
In addition, tissue dosimetry is complicated by the activity
ratios between 232Th
and its decay products.
Thorotrast is deposited at various sites in the body301.
in approximately the following proportions: liver 59%,
spleen 29%, red bone marrow 9%, calcified bone 2%,lungs 0.7% and kidneys 0.1% PO, M48].Thorium-232
has a long half-life (more than 10'' years) and decays
through a series of alpha-emitting decay products,
including 228~hand *'Rae Persons with burdens ofThorotrast adnlinistered for radiodia ostic purposes arethus continuously irradiated by B%
and its alphaemitting decay products. The estimated typical dose rateof alpha-radiation following an injection of 25 ml of69

Thorotrast in these patients is about 0.25 Gy a-' in theliver, 0.09 Gy ad in the bone marmw, 0.70 Gy a" in the
spleen, 0.16 Gy a-I in the endosteal layer of bone,
0.13 Gy a-' in the bronchi and 0.004 Gy a*' in thekidneys. (For further details, see [Cb, M481.)
A number of epidemiological studies of patients302
injected with Thorotrast have been carried out in theFederal Republic of Germany [Vl, V2, V9], Japan [Il,M10,M11, M12, M361, Portugal p 1 5 , H13], Denmark[A12, A15, F1, F2, 0 3 , 041 and the United States p].
The largest was the German study, which was started in1968. Slightly more than 5,000 patients known to havereceived Thorotrast were identified, as was a similar sized
control group drawn from the same hospitals and with asimilar age- and sex-distriiution. To reduce the influenceof any underlying diseases in the patients, Thorotrast
patients and coritrols known to have died within three
years of injection or hospitalization were excluded fromfurther study. Follow-up of the remainder was poor,
chiefly because of the disruption caused by the Second
World War, with about 1,100 Thorotrast patients and2,700 controls untraced. Nevertheless, the results that are
based on the remaining 2,334 exposed and 1,912 control
patients who could be followed until 1988 arc striking.
Among the Thorotrast patients there were 396 deaths fromliver cancer, compared with only 2 in the controls (seeTable 48). These figures correspond to a relative risk ofliver cancer of about 200. The majority of the livercancers were carcinomas, primarily of the cholangiocellular type, and haemangiosarcomas. The shortest
interval bctwcen injection of Thorotmst and dcath fionl
liver cancer was 16 years, and it seems likely that the fullburden of disease in the group has not yet become
apparenc as a substantial number of the liver cancer deaths
occurred in the most recent period of follow-up, withintervals of more than 40 years between injection andsubsequent death having been observed

In the German study the cumulative rate of303.
malignant liver tumours did not depend on age at
injection However, although there was no difference
between male and female patients with regard to age at
injection, mean volume of injected Thorotrast or exposure
time, the estimated cumulative rate of liver cancers inmales was about twice that in females, and tbe difference
was statistically significant Since the amounts ofThorotrast injected in the patients differed by a factor of
no more than two, no internal dose-response relationshipcould be derived. In the Thorotrast patients with livercancer, the three lowest doses at 10 years before diagnosis
were 1.88, 1.98 and 2.06 Gy. Risk estimates for theGerman study have, however, been calculated by taking
the cumulative number of liver tumours up to 40 yean
after injection as the numerator and the cumulative dose of
all patients up to 30 yean after injedion as thedenominator. Patients who died within the first 15 years of
exposure wen., however, excluded from the evaluation, as

70

UNSCEAR 1

they were not considered to be at risk for Thorotrastinduced malignant liver tumours. The cumulative risk ofmalignant liver tumours was estimated to be about
300 lo4 ~ y - l .
The other study ofThorotrast-exposed patients for304.
which detailed results have been presented is from
Denmark [A15 A15, F1, F2, 03, 041. A p u p of 999
patients expased for cerebral angiography, mostly between
1935 and 1947, was followed until 1 January 1989 andnumbers of incident cancers determined through linkage ofrecords with the national cancer registry in Denrnak
Many of the patients had been given angiographk
because they presented symptoms suggestive of intracranial tumours, but even when these turnours were
excluded the cumulative incidence of cancer at all othersites was estimated to reach 86% 50 years after injection
with Thorotrast. A total of 79 cases of primary livercancer had occurred, giving a standardized incidence ratio,
compared with national age-, sex- and calendar-yearspecific rates for Denmark, of 126 (see Table 49). Other
canccr sites for which them was a statistically significant
increase were liver not specified as primary, induding
haemangiosarcorna (SIR: 30); gall-bladder and extmhepatic
bile ducts (SIR: 14); leukacmia (SIR: 10); nasal cavity(SIR 10); peritoneum, i.e. malignant mesotbel ioma,(SIR 8.6); multiple myeloma (SIR- 4.6); ovary (SIR 24);lung (SIR: 23); breast ( S R 1.8); metastatic sites(SIR: 12); and cancer of unspecified site (SIR 11). Cancer
risks were also increased at most other sites, although theindividual increases were not statistically significant
305.
In a recent report on the Danish studies [A15], 16
cases of acute myelogenous leukaemia (AML)and 7 casesof myelodysplastic syndrome (MDS) were diagnosed 8-40
years after injection of Thorotrast. A multivariate model
was used to describe the response of these dyscrasias withdose (mean alpha-particlebone marrow dose, 1-34 Gy).A
risk estimate of 173 lo4 Gy-' (AML and MDS) or of
248 lo4 Gy-' (all haematological types) was derived.
Compared with low-LET estimates of leukaemia risk, thiswould be consistent with an RBE value doser to 1 than
to 20. It should be noted, however, that in many experimental circumstances, summarized for example in p 7 ]and w43], values of RBE for alpha radiation of about 20
are often found, but not for myeloid leukaemia in mice,for which low RBE values, around 3, are more often
found [U14]. Although explicit risk estimates had been
calculated only for leukaeriiia [A15], a more recent report[A16], citing 127 liver cancer cases among 1,003 patients,
derives a risk estimate of about 710 lo4 G~-',h e r thanfor other studies.

306.

The standardized incidenm ratio for liver cancer
was strongly related to injected volume, time since
injection and cumulative radiation dcse (Table 50). A
positive trend in the standardized incidence ratio withyoung age at injection was also seen, altbough the

cumulative frequency of primary liver hlmours sbowed no
diKerence between ages 0-25 years and 2645 years (seeFigure XIV). At older ages the cumulative incidence ofprimary liver cancer was lower, although the difference
was not statistically significant In contrast to the German
study, the cuniulative 6requency of liver cancer relative tothe estimakd dose in the livcr was not different for males
and females (see Figure XlV), and the standardized
incidence ratio for primary liver cancer was higher infemales (SIR: 165; 95% CI: 117-227) than in males(SIR: 102; 95% CI: 73139) [AlS].There was a clear
trend for the standardized incidence ratio for leukaemia,with the estimated cumulative radiation dose to red bonemarrow sirtiilar to that observed for liver cancer(Table 50), and there werc suggestions of positive trends
for the standardized incidence ratio for leukaernia with age
at injection, injected volume and time since injection,although they werc not statistically significant Fable 50).
There was no dvious relation between tbe standardized
incidence ratio and injectcd volume of Thorobat or timesince injection for lung cancer or breast cancer, and theauthors concluded that confounding fscbrs werc probably
responsible for the increased risk at those sites. No excess
lung or breast cancer was found in the other studies.
The Portuguese Thorotrast study involved about307.
2,500 patients injected with an average of 26 rnl ofThorotrast between 1929 and 1955 and 2,000 controls, allfollowed for 30 years [A14, D15, H131. Of 1,244 tramd
1iorotmst-exposed patients, 955 had died, 137 frommalignant tunlours (of which 87 were primary liver
turnours), 12 bom leukaemia, 8 l h m stomach carcinoma,
5 from carcinomas of the lung, 2 from carcinoma of thelarynx and 5 from prirnary bone tumours. For livercancers the average latent period was 29-34 years (forleukaemia, about 20 years), and the risk estimated in thereport of the BEIR N Committee ([C6], page 269) was
275 lo4 Gym', quite similar to the result from theGemian study.
308.
The study of Thorotrast exposures in Japan p16,
117, M10, M 11, M 12, M36] is smaller (262 cases injeaed
intravascularly, with an average of 17 ml per injection).
Follow-up has now been extended to 42-50 years post
injection There have been 56 cases of liver cancer, 6cases of blood disease, 4 cases of lung cancer, 1
osteosarcoma, 26 other malignant tumoua and 18 cases ofliver cirrhosis. With a linear dose-response model, the riskof liver cancer was estimated to be 330 lo4 Gy-'. The
Endings, time relationships, dosimetry etc were similar to
those. of the German study. The relative risk for lungcancer is cstirnated to bc 1.7 [716].

309. A much smaller study was undertaken in the
United States [F3]of 26 rases of hepatic angiasarcomas
found between 1%4 arid 1974 in Thaotrastexposed
patients. Latent periods ranged h r n 20 to 40 years. The
hepatic tuniour incidencr: is still increasing. No risk
estimate was derived for this study.

ANNEX A: EP1DEMIOU)GICAL STUDIES OF RADIATION CARCINOGENESIS

Exposure to thorium and its daughter products via
310.
inhalation has also occurred m the production of thoriumfrom monazite sand and its processing for the manufactureof products such as incandescent gas mantles. The
distribution of thorium is very different from that in
Thorohast exposure. Polednak et al. [P28] studied a cohortof men employed at a plant in Illinois between 1940 and
1973. Among 592 men who worked for at least 1 year in
selected jobs indicative of hlgb exposure to thorium and its
decay product thoron, there was a significant increase inmortality h m cancers of all types combined (SMR =1.75; 95% CI: 1.26-2.39 based on 38 deaths) (seeTable 51). There was a significant exoess of pancreaticcancer (SMR = 4.13; 95% CI: 1.349.63; based on 5
deaths), and for several other sites the number of death.
observed exceeded that expected, but since the numbers
were small, the individual increases were not statisticallysignificant
The cumulative risk of fatal malignant tumours of311.
the liver i n d u d by the alpha particles from Thomtrast
was estimated in the report of the BEIR IV Cornminee([C6], page 269), using the results of the German,
Japanese and Portuguese studies, to be about
300 10;' Cy-'. If this is divided by a w of 20, theexpected low-LFT risk is then 15 lo4 Sv-! This f i r ecompares with estimates in the report of the BEIR V
Committe aC121, page 304) of all liver cancers in thelife span study of about 18 10;' Cy-' for 40 years at risk.
However, possibly only a third of these are actually
primary tumours. More recent incidence data and revised
modelling were presented earlier in this Annex (Table 8,Part IV), and they provide improved Iw-LET risk
estimates. The risk of fatal primary liver cancer (all cases)
was estimated from the life span study mortality data to beabout 1.2 104 (PYSV)" or 48 lo4 SV-' for 40 years at
risk The liver dose-response curve for the survivors of theatomic bombings appears to be linear, however,
non-linearities at doses below 0.2-05 Sv cannot be ruledout If a low-dose-rate reduction factor of 2 is applied, thelow-LET risk estimate would be 24 lo4 SV-' for 40 years
at risk The risk estimate derived from the alpha particles(using wR = 20) is presumed to be for low-dose-rate
low-LET exposure. Thus, this value 15 10;' SV-' or somevalue intermediate between 15 10;' and about 40 1o4 SV-'
may still be the mast reasonable estimate. An additional
complication in the comparison that may be importantconcerns the age of the expased: all ages are included in
the life span study and only adults in the Thomtrast
studies.

71

patients, and it is possible that damage caused by tbe
chemical or foreign body toxicity of thorium may havecontributed to the risk of liver cancer. Recent animal
experiments suggest, however, that any such toxic effed
is likely to be small p 1 7 , W11, W12b although promotional effects cannot be discounted.

In addition to the increase in liver cancer, there313.
also appears to be a marked increase in deaths frommyeloid leukaemia in the German study, as well as in theDanish, Portuguese and Japanese studies, as noted byMole p 7 , M28].I11 the German study 35 deaths wereobserved in Thorotrast patients and only 3 among thecontrols. There were similar differences in the otber
studies. These excess cases have been estimated in thereport of the BEIR IV Committee aC6], page 272) to leadto a lifetime excess risk of leukaemia of about
50 10;' G ~ " , with a latency period of five years. Thisestimate, assuming an RBE of 10 or 20, is much less(25-5 10;' Gy-') than the low-LET risk of Ieukaemia,
which is also about 50 10;' Gy-' p10], i.e. an RBE of
about 1 would fit better for leukaemia induction fromThorotrast. However, doses are high in this study, and it
is possible that cell-killing and other factors play a role.
T h m cases of erythroleukaernia have been reported
among those exposed to Thomtrast, and it has beensuggested that high-LET radiation might specifically cause
this disease [Ma].
314.
For cancers other than liver and leukaemia,
elevated risks at a number of sites (see Tables 48 and 49)
have been cited in each of the four main studies. For
example, although relative risks and slgnifcance levels
have not been calculated for the German study, there arepossible increases in deaths from cancers of theextrahepatic bile ducts, pancreas, oesophagus and larynx
and for non-Hodgkin's lymphoma, bone sarcoma,
plasniacytonia and mesothelioma of both pleura andperitoneum. For several other sites of cancer, including
chronic lyrnphocytic leukacmia, acute lymphocytic
leukacmia, Hodglun's disease or lung cancer, no increase
was seen (see Table 49). Risk estimates could not bederived for any of these sites except bone. For bone, in thereport of the BEIR IV Committee ([C61, page 272) a
lifetime risk of about 100 lo4 Gy-l or, using a w~ of 20,
5 lo4 G ~ - ' was estimated for low-LET radiation(5 lo4 SV-' for all radiation), in good agreement withearlier quoted values.

4 Plutonium

The above risk estimates must be regarded as
312highly tentative, for several reasons. Fit,the calculations
assume linearity of risk with dose throughout except wherea low-dose-rate reduction factor other than 1 is applied.
Secondly, the dosimetry of thorium in the Thorotrast
material is uncertain. Thirdly, the liver is structurally
abnonnal as a consequence of liver damage in virtually all

Animal experiments have shown that plutonium
315.
is poorly absorbed by the oral route but slowly dissolvedin tl~ealveolar macrophages after inhalation, which meansthat the highest doses are delivered to tbe lung. Whenplutonium isotopes enter the Mood they are concentrated
in the liver and by various mechanisms at tbe bone surface

UNSCEAR 1994 REPORT72[V3], but their longer half-lives cause many of the alphaemissions to be made after the radionuclides are more
widely dishibuted within the relatively acellular calcified
bulk of the bone.

In two of the studies of nuclear workers exposed316.
to plutonium and mentioned in Section 1I.B.1,a substantial
proportion of the radiation workers was monitored forplutonium: for workers at the Sellafield plant [S14],
detailed dose estimates of plutonium are not yet available;
for workers at the Rocky Flats plant, individual plutonium
body contents were estimated fiom health physics records
based on periodic urine bioassays
The Rocky Flatsstudy induded 5,413 white males employed for at least
two years, and follow-up was to the end of 1979. The
average exlcmal dose (low-LET radiation) for the entire
cohort was 41 mGy, and the average plutonium content of
the body was 65 Bq. Mortality was compared with UnitedStates national rates for the entire group, and no excess
was found for all causes or for all cancers. Thcre werc no
deaths from bone cancer. When mortality in employeeswith body burdens greater than 74 Bq was compared withthat in employees with smaller body burdens, using lagtimes of 5 5 and 10 years, elevated rate ratios were foundfor all causes of death and for all lymphopoietic tumours.
For all causes of death these increases were notstatistically significant for any of the lag times considered,and for lymphopoietic tumours (which included one
myeloid leukaemia) the increase was signilicant only fora five-year lag time. Some other cancer sites also showedelevated rates, but none were significantly elevated. There
were no elevated rate ratios for either bone or liver cancer.
There is no clear evidence of an effect of plutonium inthis study.

m.

317.
Twenty-six men who worked with plutonium
during the Second World War under very crude conditions
at the La Alamos Laboratory have also been studied [V5,V7, Vll]. Inhalation was the primary mode of plutonium
exposure. Current estimates of the systemic plutonium
depositions in these individuals range from 52 to
3,180 Bq, with a median value of 500 Bq. The last
published follow-up included the period up to 1990. By
that time, seven individuals had died. The causes of death
were lung cancer (two cases), myocardial infardon,
artcriwderotic heart disease, accidental injury, respiratory
Eailure due to pneumonia/congestive heart failure andosteosarcoma of the sac-rum. Three men also reported ahistory of skin cancer. The man who died from osteosarcoma did not suffer from Paget's d i i , which isusually associated with bone sarcoma at older ages. In a
separatc study, all workers at the plant who had estin~atedplutonium depositions of 370 Bq or more on 1 January
1974 were identified [V6]. Of the 224 white males in thecohort, 43 had died at the time of the last follow-up
compared with 77 expected based on United Statesnational rates; 8 men had died from cancer compared with
15 expeacd.

318.
Workers in a radiochemical plant at Mayak [HI71received exposures Gum both external gamma-radiationand plutonium, about one quarter of the total exposure
being from the latter. Those in the highest dose group hadover 4 Sv total (Table 39), and a significant excess of lungcancer was noted (see paragraph 237).

5. Uranium
Miners of uranium and other ores are exposed to319.
high concentrations of radon gas and its progeny, and tbey
are considered separately in Section lTI.C. Among thoseworking above ground in the processing of uranium,
exposures to radon gas and its progeny are l w , but there
may be exposure to alpha, beta and gamma-radiation tiom
uranium compounds and progeny. A number of cohort
studies have been carried out of the health of men exposed
to utanium mainly in the fonn of UCI4 and UOj m then~lclearenergy industry [C25P241. These studies wereconsidered together with other studies of nuclear energy. !donn.B.1. No hazards SptXifin: to uranium
workers in %were identified in the cohort studies, apart Gum a suggestion in the study of workers employed at a uranium
processing plant in Tennessee during the Second World
War that men first exposed to uranium dust at the age of
45 years or older nilght be at inrreased risk of developing
lung cancer [P24]. A case-control study of men who had
worked at the plant and subsequently died of lung cancer
was performed, in which cumulative radiation lung doses
were evaluated in detail and sm0k.q status, x-ray
examinations received during employment, history of lungdiseases and potential for diagnostic radiation were
determined Go111 employee nledical records [C29]. The
study included 330 cases and 641 controls. When all tbe
men in the study were included in the analysis, there wasno suggestion of an increase in risk with increasing
exposure. However, among those aged over 45 years
wheri first exposed, the relative risk of lung cancer was
found to increase with increasing level of exposure after
controlling for age and smoking status. Among men withhigh exposures to the lung (0.20-0.75 Gy), for which a
quality factor of 10 was slygcstd in the paper (meanequivalent dose: 275 Sv) [B32], there was a fourfold
inc~easein lung canter risk (based on 11 cases and 6
controls), and this increase was statistically significant It
is possible that tliese findings indicate an increased risk oflung cancer among men exposed to uranium dust HOWever, it is also possible that the increase is a chancefinding based on subset analysis or inadequate control forsmoking.
Uranium millers are also exposed to a i h e dust
320.
containing 2 3 4 ~2, 3 8 and~ 5.
Two studies of uranium
millers have been c a d out [All, W191. In both studies
the number of dcaths observed Erom lung cancer was lessthan expected, arid neither study reported an excess ofbone cancer. However, both studies reported an excess of

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

cancers of lymphocytic and haematopoietic tissue otherthan leukaemia (4 observed, 1 expected in the entire
period [All]; 6 observed, 2 6 expected m the period morethan 20 years after commencement of employment[W19D. The observed deaths comprised giant follicularlymphoma (two), multiple myeloma (two),lymphosarcoma (three), and Hodgkin's disease (three).

6. Polonium
321.
A cohort study of 4,402 white males employedby the Mound facility in the United States during theperiod when poloniunl operations were conducted (19441972) has been carried out [W13]. Overall, no excess
mortality was observed, but among workers initially hired
during the Second World War, mortality was elevated,
especially for deaths fiom all cancers, cancers of the lungand cancers of the rectum. However, these increases did
not appear to be related to exposure to *lOpo. Amongworkers monitored for 'lO~o,mortality was significantly
less than expected, although more lung cancers wereobserved than expected. In this subcohort, no significant
dose-response trends were identified for all calrwr
combined, all cancers combined or cause-speciEic cancers.

7. Summary
322
There is overwhelmin evidence that bonesarcomas can be induced by both "Ra and the long-lived
isotopes of radium incorporated into the body a k r
injection or ingestion. Because of the short half-life of='Ra (3.6 days) and the relatively short duration ofadministration, the study of patients injected with it has
been informative in revealing the time pattern in which theradiation-induced tumours occur. The excess risk appears
to start about 3 years after exposure and to last for about
30 years, with the excess absolute risk reaching amaximum 6-8 years after exposure. Excess absolute risks
per gray do not appear to depend strongly on sex or age
at exposure. Further analyses of the data in terms of therisk of asteasircoma per person-year at risk in conjunction
with dose, treatment period, time since exposure and otherfactors would be helpful in enabling comparisons with therisks seen in other populations following other types of
exposure. The excess absolute lifetime risk of fatal bone
cancer derived fim these high-LET exposures is
estimated to be 5 lo4 SV-' for both high- and low-LET
radiations.
323.
Studies of dial painters and others who
accumulated bod burdens of %a and 228Ra confimi th,
findings of the R'aseries of a relatively short minimum
induction period after first injection or ingestion
Dose-response relationships have been more difficult toevaluate than among patients exposed to 24Ra. Two-stepmodels have been invoked to explain the obsexvations.

73

However, the available data do not appear to have been
fully exploited, and further epidemiological work,
including more refined dosimetry and statistical analysis,
would be informative.
324.
The only other cancers that are clearly attriiutableto radium are those of the paranasal sinuses and mastoid
air cells, which occurred 20 and more years aticr
commencement of exposure in persons with body burdensofand 228Ra in the United States. Furtber dosimetry
and analyses of the available data would allow the existingrisk to be bener described. There is some evidence of anincrease of leukaemia and of breast and liver cancer inpatients treated with z4Ra. Increases of some cancers indial painters in the United Kingdom and in the UnitedStates may have resulted hom external gamma-radiation.
The further study of these increases and the associateddosimetry, including the role of external gamma-radiation,
would be informative.
325.
Then: is ove~whelmingevidence that injectedThorotrast causes liver cancer and leukaemia, and it seems
likely that it also causes a variety of other cancers. For
liver cancer the minimum latency period is about 15 years
since f i t injection, but for leukaemia it is shorter, no
more than about 5 years. Both the excess ahsolute risk andthe excess relative risk of liver cancer increase as theamount of Thorohast injected increases. The excess
relative risk of liver cancer is higher in those injected atyounger ages, but the excess absolute risk does not appear
to depend strongly on age at exposure. For a given
admmistercd amount, males and females have similarrisks. Based on the German, Japanese and Portuguese
studies, the cumulative risk of liver cancer is estimated to
be about 300 lo4 G~-'. This implies a low-LET risk of
15 lo4 G ~ - (wR' = 20), or 15 10" SV-' for all radiations,which is broadly comparable with risk estimates h m lowLET exposures detennined from the life span study (Table5). It should be noted, hwevcr, that although theseestimates of liver cancer risk are attributed to the alphapartides of thorium, the chemical effects of thorium may
also enhance the radiation risk. On the other hand, thedoses are high, and with cell-killing and other factors
potentially involved, the risk estimates may be lower thanthose for l w c r doses. The excess of leukaemia among
patients treated with Thorotrast appears to be concentrated
among tuniours of the acute myeloid type (including a
relatively large number of the rare erythroleukaemias) it
is, however, small compared with the low-LET risks
derived from the survivors of the atomic bombings, i.e. it
is compatible with an RBE closer to 1 than to u3 for thisend-point The risk of osteosarcorna is similar to risks
derived from z4Ra exposures.
326.
The information contained in the studies of theeffects of Thorohast has not yet been fully exploited, andadditional analyses would be helpful. For example,
dose-response analyses based on the number of liver194 REPORT

tumours per petson-year at risk, classified by total dose
accumulated up to 10 years previously and other relevant
fsctors, would allow an examination of the shape of thedose-responx curve in the German study, as well as acomparison with the results of other studies. In theGerman study, relative risks and significance levels forcancers other than liver cancer have not been calculated
and would be informative, as would explicit risk estimatesin the Danish, P o m g u s e and Japanese studies.
The studies of men occupationally expared to327.
other radionuclides, e g . polonium and uranium, suggestthat these exposures may be associated with increased
risks of specific types of caner, but the studies are smallin size and at present have only a limited length offollow-up. Further information is necessary before definite
conclusions can be drawn
The question of whether high-LET alpha radiation328.
induccs tumouis other than those caused by Iw-LET
radiation or more fiquently than would be expected basedon values of RBE or of the radiation wetghting factor is
not completely answered by the information available so
hr. Liver cancer risks from high-LET and low-LET
radiation appear to be broadly similar in spite of age andother differences m the populations exposed. The increases
in deaths from myeloid leukaemia in the Thorotrast studies
are clear-at, but risk estimates are less than expeded
Eroni low-LET risk estimates unless an RBE closer to 1
than to 20 is used.
329.
Risk estimates for bone cancer induction(5 lo4 SV-l) are dexived from studies of 2 4 ~ a but
supported also by the Thorotrast studies. Risk estimates forliver cancer (15 l o 4 s f 1 ) from the Thorotrast studies arebroadly similar to risk estimates derived bom studies of
low-LET radiation.

Nunrerous studies of underground miners exposed330.
to radon and its decay products in the air of uranium andother hard rock mines have shown an increased risk oflung cancer in comparison with non-exposed populations.
The subject was reviewed m the UNSCEAR 1 9 n Report[US], in which it was estimated h a t tbe number of lungcancers caused by exposing 1 million people to 1 WLM(equivalent to 5 mSv [118l) would be 200-450, comparedwith a natural rate of lung cancer of 10,000-40,000 per
million people in a lifetime. In the UNSCEAR 1988
Report [U2], the range estimated was similar. Radon isclassified as a GToup I carcinogen by the International
Agcncy for Research on Cancer p19]. The recognition
that hard rock miners face an occupational risk has
resulted in reduced exposure levels in many such mines.
However, in r a n t years other impottant sources of
exposure to radon have been remgniixd; for example, it

is now established that in places where air exchange withoutdoor air is restricted, especially in homes, offices andother buildings, radon may accumulate in appreciable concentrations. In rcsponsc to the need to conserve energy
used for heating, construction methods that improve insulation and sharply restrict ventilation have been introduced
in sonic countries (for example, Sweden), increasing thc
radon exposure of the general population There are now
a large number of investigations of tbe risks associatedwith non-occupational exposure to radon, as it is a subjectof considerable public concern in many countries.

1. Occupational exposum
The principal sources of quantitative information
331.
on Ule effects of exposure to radon remain the occupational studies of miners of uranium and olher hard rock.
For some studies (e.g. v 3 , TlOD detailed exposure
histories arc available, but for many others the exposure
history of individual miners is not known p e c k l y , so theestimates of individual exposure are subject to considerable error. Another difficulty arises when attempts are
made to generalize to the population h m the results ofthese studies: HI all of them the exposures are expressed in
tern= of working level months
The dose to thebronchial epithelium varies somewhat with lhe fraction of
unattached radon pmgeny in the air and with the breathingrdte. Minc exposure levels have been reduced over timeand cuniulative exposures in most countries no longer
exceed 100 WLM. Interest now f o c u s on. the possible
effects of lower exposures of more recent workers, but
further results are still expected from study of the higber
exposures received in the past
332.
Since the last review of tbe subject by theCommittee in the UNSCEAR 19?7 Report [U5], a numberof other groups have used data 6om the studies of
exposed rniners to estimate the lifetime risk of lung cancer
mortality following lifetime exposure to radon progeny. In
one study, the BEIR 1V Committee [ a ] obtained detailed
tabulations of data from four of tbe principal cohort
studies and carried out extensive statistical analyses. Dataon individual smoking habits were not available h m all
four studies, and the Committee ma& the implicit
assumption that the joint effect of cigarette smoking andradon was multiplicative. Their findings indicated that therisk of lung cancer mortality was best explained by amodel HI which the excess relative risk was directiyproportional to the cumulative exposure, but m o d i f d by
the age at which the risk occurred and by the length oftime sincc exposure. The excess relative risk decreased
with atlained age and declined with increasing time since
exposure.
also considered
The BEIR IV Committee [a]333.
the distribution of lung cancers by specific histologjcal
type and concluded that the greatest excess was found forANNEX A: EPIDEMI0U)GICAL S?UI >IES OF RADIATION CARCINOGENESIS

smallcell carcinomasbut that other histological types werealso inmsed. More recent work includes a study in
China v 6 ] , in which a s~gnificantdose response foradenocarcinoma was found However, a different result
has been found in a r a n t comparison of lung cancer
induced in miners and in survivors of the atomic bombings [L23]. This study, conducted by a team of Japaneseand American pathologists, found that radiation-induced
cancers were more likely to be small-cell cancers thanadenocarcinomas. A sigwificant dose response was foundfor small-cell cancers for both the miners and thesurvivors of the atomic bombing.
334.

Since the publication of tl~ereport of the BEIR

IV Committee [a]a,number of new studies of lungcancer in miners exposed to elevated levels of radon havebeen camed out [C31, H16, H37, L17, M18, R9, S5, S24,
S57, S58, T3,T9,T10, W1, XI]. Two of these studies,
one on Chinese tin miners [XI], the dher on West
Bohemian uranium miners [S57, T3], each included alarger number of lung cancers than had been included in
all four datasets available to the BEIR IV Conlmitlee for
their review. They have thus enabled the appropriatenessof the model used by the BElR IV Committee [a]to beexamined. Both new studies included a substantial amountof information on the effects of exposures more than 15
years previously, and the finding with respect to variationin the excess relative risk of lung cancer per unit exposure
with time since exposure are summarized in Table 5 2Both find clear evidence that the effect of exposures in the
distant past is less than the effed of more recent
exposures. In both studies, the excess relative risk per unit
exposure for exposures 15-24 years previously is about
half that of exposures 5-14 years previously. In bothstudies, the effed of exposures received 25-34 years
previously is less than that of exposures 15-24 years
previously, and exposures more than 35 years previously
have little effect
These two studies also find strong evidence that335.
the excess relative risk per unit exposure varies withattained age, as can be seen from Table 53. In the Chinese
study, estimates of the excess relative risk per unit
exposure, including the entire follow-up period, indicate a
25-fold variation in the excess relative risk per unit
exposure with attained age. In the West Bohemian study,
estimates specific to the period 5-14 years since exposure
indicate that the excess relative risk per unit exposure atages 35-44 years is twice the value for attained ages of 55
years and above, and at ages <35 years it is elght times as
great. The two studies, therefore, independently confirm
two of the conclusions of the BEIR IV Committee [C6],namely that the effect of radon exposure is concentrated
5-14 years after exposure and that the excess relative riskof lung cancer per unit exposure decreaseswith attained age.
Recently a joint analysis of data from 11 studies336.
of male underground miners was conducted P I ] . Over75

2,700 lung cancer deaths occurred among 68,000 miners
who provided nearly 1.2 million person-years forobservation Fable 54). The mines were in Australia,
Canada, China, the former Czechoslovakia, France,
Sweden and United States. The exrelative risk of lungcancer was linearly related to cumulative expasure toradon progeny, estimated in WLbUL. The excess relativerisk per unit exposure in the combined data was
0.49% WLM-'(Table 54). As in the analysis carried out
the excess relative riskby the BEIR IV Committee [a],per WLM was strongly modified by various factors. It
decreased with attained age, with time since exposure andwith time after cessation of exposure to radon. Amongminers f i t exposed to radon in the mines when they wereless than 20 years old and less than 10 years old, 861 and110 lung cancer deaths were observed However, theexcess relative risk per WLM was not related to age at
Erst exposure. Over a hoad range of total cumulative
dose, higher lung cancer risk was associated with
underground exposures received at low rates, suggestingthat either low exposure rates or long duration of exposure, or both, may be especially hazardous (Figure XV).
It is difficult to interpret the data on lung cancer
337.
in miners because of the confounding effects of cigarettesmoking and exposure to other carcinogens in mine air,such as arsenic. The joint effects of exposures to radonand other agents are considered in Sedion III.C.3. Twostudies, both of uranium miners in the Colorado Plateau,have demonstrated that exposure to increased levels ofradon gives rise to an elevated risk of lung cancer, evenwhen few or no cigarettes are smoked.
The first of these studies used data 6om the New
338.
Mexico tumour registry in a population-based case-control
study of lung cancer in Navajo men [S25]. The 32 casesof lung cancer included all those oocuning among men
between 1%9 and 1982 For each case, two deceased con~ o l withs non-respiratory cancer were seleded Of the 32
cases, 72% had been employed as uranium miners, whereas no controls had documented experience in this industry.
The lower 95% confidence limit for the relative risk oflung cancer associated with uranium mining was 14.4.
Information on cigarette smoking was available for 21 of
the 23 affected uranium miners: 8 were non-smokers, andthe median consumption by the remainder was in therange 1-3 cigarettes per day.
The second study of lung cancer among non339.
smokii uranium miners was carried out by the UnitedStates Public Health Service on 516 white men in thecohort of Colorado Plateau miners who were reaxded asnever having smoked cigarettes, pipes or cigars [R9J
Follow-up was carried out from 1950 through 1984. Agespecific mortality rates for non-smokers 6om a UnitedStates study of veterans were used for comparison
Fourteen deaths from lung cancer were observed among
the non-smoking miners, while 1.1 deaths had been

UNSCEAR 1993 REPORT

76

expected, yielding a relative risk of 1 2 7 (95% CI: 8.0-20.1). The median exposure in this group was 2% WLM(mean 720 WLh4).
Data on tobacco use were available for 6 of the340.
11cohorts analysed by Lubin et al. F21]. No clear pauernof risk for the joint association of smoking and exposure
to radon emerged, although the data were most consistent
with a relationship that was intermediate between
multiplicative and additive. In cohorts with information on
the use of tobacco,64 lung cancers occurred among nearly
3,000 non-smoking miners. Analyses revealed a linear
exposure-responsetrend that was about three tin~eshlgber
in never-smokers than in smokers. Data on exposure toarsenic was available for two cohorts. Exposure to arsenic
inaeased the risk of lung cancer, and adjusting for it
reduced the estimated excess relative risk per WLM.

t. Effect of exposure mte
341.
Substantial evidence has emerged in recent yeanthat among miners exposed to high concentrations ofradon, higher excess relative risks per unit dose areassociated with a lower average exposure rate and/or alonger duration of exposure. The effects of these two
factors, exposure rate and exposure duration are often
difficult to disentangle and express separately. The reasonsfor a higher risk at lower exposure rate or longer duration
are unclear. Possible explanations include random orsystematic errors in estimates of exposure rate, a nonlinear relation between exposure and dose to the target
cells at high exposure rates, cell-killing at high exposure
rates, and effefects related to the multistage nature ofcarcinogenesis.
342
The initial evidence of the exposure rate effect
was put forward by Howe et al. p 1 5 , HI61 in studies of
the workforces of two Canadian uranium mines, both
operated by the former Eldorado Resources Ltd. In thek t study, of workers at the Beaverlodge niirie in
Saskatchewan, the excess relative risk per unit exposure
was initially given as 3.28% WLM-' (95%CI: 2084.48).
A re-evaluation of a sanlple of the dosimetry data at the
Beaverlodge mine has indicated, however, that there wasconsiderable underestimation of the exposures and that theinitial risk estimates should be multiplied by a factor of
0.65 [H23]. A further re-evaluation of exposure histories
in this study is under way. Using the currently available
factor of 0.65 gives an excess relative risk per unit
exposure of 213%
(95% CI: 1.35-291). In thesecond study, of workers at the Port Radium mine in the
Northwest Territories, the excess relative risk per unit
exposure was about one eighth of this value, or
0.27% WLM-' (95% CI: 0.11-0.43). When expressed interms of excess absolute risks, the contrast between thefindings for the two mines is also strikmg: the risk was
1 3 5 10' PY-' WLM-' at Beaverlodge (95%CI:7.67-19.4)

after allowing for the revised dosimetry, while it was
3.10 loa PY-'WLM-I
at Port Radium (95% CI:
1.89-4.32). The chief dirference between the two mines
seems to be in the average exposure rates, which were
estimated to be 8 WLM a" at Beaverlodge after allowing
for the revised dosimetq and 109 WLM a'' at Port
Radium.
343.
The question of an increased carcinogenic effectper unit exposure for lower exposure rates or longer
duration times has arisen in connection with other highLET exposures and is widely known as the "inverse d m rate effect". The word "inverse" is used because the effeea
of dose rate is inverse to that usually found with law-LET
radiations, where higher dose rates are almost always more
effective than lower dose rates Tbe phenomenon incellular transformation systems [HI41 and a possible biological basis for it involving the initiation of carcinogenic
steps at only one brief portion of the cell cycle [R3] havebeen widely discussed (see, for example p 1 3 , S30D. The
effect is not seen in all circumstances. The possible
biological basis for the effect has been elaborated in aniodel that appears to account for most features of theeffect (B10, U1 (Annex F)].
344.
Evidence that higher excess relative risks per unit
exposure are associated with lower average exposure rates
in miners has also been reported in three other cohorts.
First, Hornury and Meirihardt [H18],in an analysis ofdata from the study of uranium miners in the Colorado
Plateau, found statistically significant evidence of an
exposure rate or duration effect, implying that amonggroups of miners receiving equivalent cumulative
exposures, those exposed to lower levels for longer periodsof time were at greater risk of lung caner. They also
found that this effect varied with cumulative exposurelevel. Thus a miner with total exposure in the range
0-830WLM at a rate one tenth as greatas another minerof the same age, smoking status and cumulative exposure
would have a 58% greater risk of lung cancer. Secondly,in the cohort of Chinese lin miners the excess relative risk
per WLM declined smoothly with increasing exposure ratefrom 1.74% among miners exposed at less than 10
WLM am'to 0.48% among those exposed at niore than 30
WLM a-I [XI],as is summarized in Table 55. Whenthese risks are adjusted for arsenic exposure, which may
be correlated with radon exposure, there is still a small but
consistent decrease in excess relative risk with increasing
exposure rate. Thirdly, k v c et a]. [SS, SS7] reported asimilar effect within the cohort of miners in the former
Czechoslovakia. However, it should also be noted thatsome studies IT101 do riot find that risk increases with alower exposure rate.

345.
Some additional evidence comes fim acon~parisonof estimates of risk derived bonl the fourcohorts of niiners studied by the BElR N Committee[C6]. These and other estimates are presented in Table 56.

ANNEX A: EPIDEMIOLOGICALSTUDIESOF RADIATIONCARCINOGENESIS

Beavedodge was among the cohorts studied. Results forworkers at the Port Radium mine were not available atthat time, but they are shown in the Table for the sake ofcomparison, as are the recent results for Newfoundland,
Cornwall, China, former Czechoslovakia,France and New
Mexico. The estimates of risk calculated by the original
authors are given in Table 56 along with the estimatescalculated by the BEIR IV Committee [C6]in one of theirjoint analyses. Values given by the original authors may
not bc comparable as the different studies covered
different ages and follow-up periods. The estimates of the
BEIR IV Committee [C6] are specific to age 55-64 years
and lo exposure in the preceding 5-14 years and thus takeaccount of the different age-structures and follow-up
periods in the different studies. Miners at Malmbcrget had
exposure rates comparable with those at Beaverlodge andalso experienced hlgh excess relative risks per WLM.
Miners in the Colorado Plateau had exposure rates similar
to those at Port Radium and experienced lower risks per

WLM.
The above evidence suggests that lower exposure346.
rates, i.c. longer durations, are associated with higher risk
per unit dose. This issue has been investigated furiher ina special study of the effect of exposure rate in the cohortof West Bohemian uranium miners [T3]. Using detailed
information on the dates during which each man in thecohort worked in the 19 mine shafts involved, together
with 39,000 shaft- and calendar-year-specific radonmeasurements, the exposure rate experienced by cach man
in each month of his employment was calculated. The
effect of variations in exposure rate was then studied using
power transformations of the monthly exposure rates.
When data hthe entire cohort were considered, models
constructed in this way provided a substantially better fit
to the data than models based on cumulative exposure in
the usual way, and they confim~ed that exposuresdelivered at higher exposure rates (i-e. over shorter times)
were associated with lower excess relative risks per unit
exposure. Among the class of models studied, the bestfitting model was obtained by taking a square-root
transformation of the monthly expaure rates. In thisanalysis, miners wcre enrolled in the study five years a k r
starting underground work. During those Erst five years on
the job, some of the men had worked in shafts whereconcentrations exceeded 10 W L However, the high radon
concentrations did not persist more than f i e years a k r
the men had started underground work, and they now
occur only very exceptionally, eilllcr occupationally or
environmentally. The analysis was therefore repeated, thistime including only men who had never worked in shafts
where the radon concentration exceeded 10 W L When
this was done, the excess relative risk per WLM did notvary with e x p u r e rate or with calendar year, age at startof underground work or duration of exposure. in addition,
there was no evidence of non-linearity in the excess
relative risk with time-weightcd cumulative expasure. The
exccss relative risk per WLM estimated by consideringnonly men who worked in shafts with radon concentrations
below 10 W L was just over twice that estimated fiom theentire cohort [ D l . If this is confirmed in other studies, itwould be more appropriate to base risk predictions fordomestic or modem occupational exposure on theexperience of men exposed only at lower rates of exposure(much less than about 10 WL). The variations in excess
relative risk with time since exposure and attained age for
the West Bohemian miners exposed to less than 10 WL
are given in Table 57.

3.

Other issues: cigarette smoking,arsenic and cancer at otber sites

347.
The joint effects of exposure to radon andtobacco smoke in uranium miners were discussed briefly
in the UNSCEAR 1982 Report p 4 ] in a general reviewof the effects of exposure to radiation m conjunclion withother carcinogenic agents. Since then a number of additional reports have become available, and the subject has
been reviewed by Lubin PI.The available data, however, have many limitations. Not only are the histories of
exposure to radon not well known for individuals, but
obtaining accurate cigarette smoking histories is often
difficult. In addition, the resulting risk may well bestrongly dependent on hctors other than tbe total exposure
to radon or cigarette smoke. For example, laboratory
experiments with rats have shown that radon followed bysmoke is four times more hazardous than the same
exposures given in reverse sequence [GI31
The BEIR IV Conunitlee [C6] analysed the com348.
bined effects of exposure to radon and cigarette
consumption in two populations of uranium miners. For
Ihe fiat of these the Cor~lmittceobtained access to an
on-going cdse-control study of lung cancer in a cohort of
New Mexico uranium miners. The cohort included 4,051
subjects with at least one year of documented undergroundemployment. The cases included all Hispanic and nonHispanic white males diagnosed with lung cancer. For
cach of the 69 cases, four controls were selected The
number of years of employment was used as the measureof exposure to radon, and cigarette smokmg histories forboth cases and controls were available 6vm prc-employrnent or annual physic21 examinations. The data werefined with models in which the relative risk of lung cancer
was either multiplicative ui the two exposures (relative risk
= (1 + ar) (1 t hs), where r is years employed as a minerand s is number of cigarettes per day) or additive (relativerisk = 1 + ar + bs). The results suggested that the multiplicative relative risk model gave a better fit for the data,
although there was not a statistically significant difference
between the fit of the additive and multiplicative models.
M e r the public2tion of the report of the BEIR IV
Conlnlittee [C6]the original investigators carried out a fullanalysis of the New Mexico data using individual
estimates of exposure to radon progeny rather than years

78

UNSCEAR 1994 REPORTof employment [S24, S58]. They did not find evidence ofa departure from a multiplicative interadion and concluded
that the combined risk of the two agents was adequately
d m i d by the product of the individual relative risks.
The joint effects of cigarette smoking and radon349.
in uranium miners in the Colorado Plateau have also beenstudied in detail. Whittemore and McMillan w ] , using
data up to 1977, showed that an additive relative risk
model of the form described in the p c d i n g paragraphgave a poor fit to the data, while a multiplicative model
could not be rejeded The BEIR IV Committee [C6]extended this analysis and applied it to data up to 1982
Their findings supported the conclusions of Whittemoreand McMillan The Committee also fitted the data withsome general risk models and found that they wereconsistent with a wide range of submultiplicative tosupra-multiplicative models. They found no clear reason
except parsimony to accept precisely the multiplicativemodel. In another analysis of the Colorado data through1982, Homung et al. [HI81 concluded that the effects ofthe two exposures wcre better modelled using powerfunctions (using the notation of the previous paragraph,
relative risk = ?sb and relative risk = P + sb for multiplicative and additive forms, respectively) rather thanlinear functions. When this was done, the joint effect of
exposure to radon progeny and cigarette smoking was
greater than additive but slightly less than multiplicative.
The departure from niultiplicativity was not quite
significant (p = 0.06), and the authors showed that theevidence of sub-multiplicativity came chiefly from data inthe most recent follow-up period, 1977-1982
350.
Sevcn further studies of miners in Sweden (threestudies), former Czechoslovakia (one study), China (onestudy) and Canada (two studies) present data on the joint
effects of cigarette smoking and exposure to radon Of theSwedish studies, the first, which presents data from
Hammar, suggested a protective eff& of smoking thatmight be attributable to smokers having a thickened
mucous layer in critical bronchial regions [A7]. The study,
however, was small (29 cases), and the results may havebeen biased, as mine foremen were the sourcx of smoking
status for miners. Moreover, controls may have included
persons who died from tobacmrelated causes [C6, LS].
The second Swedish study presented data from
Malmbergct and included data on 51 lung cancer deathsp8]. After a complex series of assumptions it wasestimated that the relative risk for non-smokers was 10.0,
while that for smokers was 29. The authors concluded
that mining- and smoking-related risks combined
additively. However, as noled by both the BEIR IV
Committce [C6] and by Lubin [LS],this conclusion seems
to go beyond the evidence as presented, and the estimatedrelative risks appear compatible with a joint model that isgreater than additive but less than multiplicative. The third
Swedish study, from Kiruna and Gallivare, was acase-control study and included 60 lung cancer deaths[D13]. Among non-smokers and smokers with lifetime
cigarette consumptions of less than and m a e than 150,000
cigarettes, the estimated relative risks f a those with nounderground mining experience were 1.0, 24, and 8.4,
respectively, while in the same smoking categories therelative risks for underground miners wcre 5.4, 21.7, and69.7, respectively. Thus the results appear consistent witha multiplicative relative risk model, although no formal
testing was carried out

A nested case-control study has been canied out
351.
within the cohort of Beaverlodge uranium miners to asscss
any possible contribution of confounding by smoking andother mining experience to the risk estimate derived fromthe original cohort study PlS]. Next of kin wereinterviewed for 46 lung cancer cases and 95 controls
enrolled in the original study who had died between 1950
and 1980. Controls were rtiatched to cases by province ofdeath, year of birth and year of death. The data wereanalysed using conditional likelihood methods and linear
logistic models. An initial model included terms
representing cumulative radon exposure lagged by fwe
years and number of cigarettes smoked per day. When athird tern1 representing the interaction between these two
eflccts was included, its estimated coefficient was small
and negative and its 95% confidence interval induded
zero. Thus the data showed no significant departure horna multiplicative effect of radon exposure and cigarettesmoking, although the best-fitting model indicated that the
combined risk of the two agents was slightly less than the
product of the individual relative risks.
352.
In the study ill former Czechoslovakia [S5],smoking data were available only for clay shale miners.
Three deaths occurrcd among non-smolung miners
compared with 0.3 expected according to nationalmortality rates; for miners who smoked, 19 deaths wereobserved compared with 11.7 expected. On that basis therelative risks among non-smokers and smokers were 10.0
and 1.6, respectively, while the attniutable risks (exass
dcaths) were 16.6 and 26.1 10' PY-I WLM-',
respectively. In the Chinese study [XI], the smoking
information was liniited to method of use and there wasa substantial amount of missing data. Nevertheless, theanalyses rejected both additive and multiplicative
relatio~isllipsbut were consktent with a range of models
i~itcnnediatebctwecn additive and multiplicative. Finally,in the Canadian study of fluorspar miners w18], theexcess absolute risk coefGcients among t h a e who neversmoked (based on 7 deaths) and among current smokers(based on 57 deaths) were very similar at 7.6 and
6.3 10-6 PY" WLM-' , respcctively. A few of the studies
of non-occupational exposure to radon have presented data
separately for smokers and non-smokers [U, L1, Sm].
These suggest that the joint effects of cigarette smoking
and radon are more than additive. However, they do not
yet provide enough evidence to allow a detailed
examination of the alternatives.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

353. W e n all the data on the joint effects of cigarettesmoking and radon are considered, there is ample confmmation of the conclusion of the BEIR IV Con~mittee[C6],namely, that the joint effect of the two agents is more thanadditive. However, there is a mounting body of evidence
that the effect is somewhat less than multiplicative. The
strongest evidence for this conclusion comes 6om the twostudies of non-smoking miners [R9, S25) The relative
risks reported in those studies are substantially hlgher than
the risks reported in studies that included smokers.
However, some corroborative evidence of submultiplicativity is also available from the most recent analysis of theColorado miners [H18],from the Newfoundland fluorspar
miners [M18],from the clay shale miners in former
Ckechoslwakia [S5]and irom the Malmberget study w ] .
It should also be noted that for low-LET radiation the joint
effects of smoking and exposure to radiation from theatomic bombings of Hiroshima and Nagasaki appear to beless than multiplicative for lung cancer. Recent work invitro on the interaction between high-JJ3 radiation andtobarn smoke condensate also suggests an interaction for
the end-point ofonmgenic transforniation that is less thanmultiplicative P I . The implications of this conclusion
are hr-reaching, in so far as predictions based on models
in which multiplicativity between radon and cigarettesmoking is assumed, either implicitly or explicitly, cangenerally be assumed to be too low for populations inwhich there are substantial numbers of non-smokers,
including many populations of women, and too high for
populations with hlgh proportions of smokers.
354.

In the study of Chinese tin miners [XI],thearsenic content of the ore averaged about 1.34% by
weight Thus, many of the miners were exposed to dusts
containing arsenic, which is a known carcinogen [ES,I191
As can be seen from Table 55, adjustment for arsenic
exposure reduced the estimated relative risk of lung cancer
within each category of cumulative radon exposure inthese data, and the estimate ofthe excess relative risk perunit exposure, averaged over the entire follow-up period,
was reduced from 0.6% WLM-I (95% CI: 0.40.8) to
0.2% WLM-'(95% CI: 0.1-0.2). In Ontario gold miners
N O ] an excess lung cancer risk could not be attributed
to radon exposure alone and was associated with exposure
to arsenic in the mines.

355.

The miners of the West Bohemian cohort were
employed in two separate mines: JBchymov, with arseniclevels of 05% in the dust on average (7.1% maximum),and Horni Shavkov, in which arsenic was negligible, i.e.
average concentrations of 0.01% in the dust (0.05% maximum). While no comparison was possible between miners
employed exclusively at one or the other mine, in miners
who spent less than 20% of their time at Jachymov andwho were 55 years old or more the excess relative risk oflung cancer was 1.36% WLM-' 5-14years alter exposure(Table 57), similar to the value derived by the BEIR IV
Committee [C6]of 15% WLM-I.
However, for similar

79

miners with more than 20% of their work experience at
JAchymw the excess relative risk was 1.8 times greater,
indicating a clear effwt of arsenic exposure (Table 57).

356.

The effeds of exposure to other agents in miners
exposed to radon has received little attention in theliterature up to now, but these results suggest that exposure
to arsenic-containing dusts may have an important
influence on the subsequent risk of lung cancer in somegroups of miners exposed to radon, and further evaluationof this possibility is required Mine exposures other thanarsenic might also influence tbe risk of lung cancer either
directly or indirectly, possibly via mechanisms related tocellular irritation and increased tissue proliferation [C21].
The role of dust (silica), diescl and blasting fumes andother heavy metals has also not been clearly elucidated
and requires additional study.

357.

Significant increases have been noted for certain
cancer sites other than the lung in miners exposed toradon. These include salivary gland cancer in Newfoundland fluorspar miners w18], laryngeal cancer in Frenchuranium miners (TlO],multiple myeloma, cancer of thestomach and cancers of the liver and gall-bladder in
Swedish iron-ore miners [R8],basal cell skin arcinonla
in mid-Bohemian uranium miners [S64] and cancers of theliver and gall-bladder and extrahepatic bile ducts in West
Bohemian uranium miners PI.However, no consistency
exists across studies, and many of the reported incream
may not be related to radon exposure. In the West
Bohemian miners [Dlmortality was related to cumulative
radon exposure only for cancers of tbe gall-bladder andextrahepaticbile ducts and multiple myeloma, while in tbc
Chinese tin miners a significant but weak relationshipbetween mortality and a joint association of exposure toradon and arsenic was found only for lymphoma [XI].
Neither of these two studies of miners nor a small casecontrol study of domestic radon and childhood cancer in
Sweden [ S Z ] found evidence for an increased risk ofleukaemia following radon exposure.

358. It has been suggested h m geographical correlation studies that radon in the ambient air may cause
cancers at sites other than the lung pl, E9, H38, L8,
W6]. It has also bcen suggested that the dose received
from radon by the red marrow is hlgher than that usuallyestimated because radon is very d u b l e in the tat cells
scattered throughout the marrow [R17J. Other informationon the dose to organs other than the lung is also available[H47l.These correlation studies are subject to numerous
biases, however. Interpretation is r e s t r i d by the fsct that
exposure to individuals, much less dose to tissues, is notknown. Furthermore, attempts to reproduce findings (onleukaemia, for example) using more refined statisticalmethods and smaller geogaphical areas have not been
productive p13]. Thus, there is no reproducible evidence
that radon causes any increase in fatal cancers other thanlung cancer.

UNSCEAR 1994 REPORT

80

4Residential exposures

Although the studies of occupational exposure toradon provide a guide to the likely effect of exposures inhonies and other buildings, there is inevitably a substantial
degree of uncertainty in extrapolating between the twoenvironments. One reason for this is simply that theoccupational studies provide data about the effects of
exposure primarily in adult males and give no information
about effects in women, who in many populations havesubstantially different smoking habits from men, apartfrom intrinsic differences in, for example, breathing rates.
or about the effects of exposure in early childhood.
Another source of uncertainty arises fiom dimerenm
between mines and the indoor environment regarding
several factors that affect the dosimetry of radon decay
products, including ventilation patterns; the fraction of
unattached radon decay products and the partide size
dish-iution in inhaled air; the equilibrium between radonand its decay products; and differences in the breathing
rates and breathing route (nose versus mouth) of men atwork and at home. As already noted, the effects of mine
exposures are subject to confounding or enhancing frommine contaminants such as silica, arsenic, diesel exhaustand blasting fumes [A17].
359.

360.
It is therefon: necessary, despite the technical andmethodological difficulties involved, to directly examine
the effects of exposure lo radon and its decay products in
the indoor environment. The published results of studies
addressing this issue are summarized m the following
paragraphs, based on a review by Samet [SB]. Many
more studies are currently under way, and much additional
infonnation on this topic should soon become available. In
most studies of indoor radon, the concentrations aremeasured in becquerel per cubic meter. The conversion
hctor between radon gas concentration in ctwellings andeffective dose was considered in Annex A of the
UNSCEAR 1993 Report [Ul].It is noted, however, thata committee of the National Academy of Sciences of theUnited States [C21] concluded that the dose per unit
exposure tends to be 20%M% lower in the homeenvironnient than in the mines. Thus, risk estimates basedon the experience of miners will tend to overestimate risb
fiom radon in homes [C21].

361.
Several studies of non-occupational exposure toradon have been camed out in which lung cancer
incidence or mortality rates in different geographical areas
have been correlated with measures of exposure of the
inhabitants. These are summarized in Table 58. In 8 of the
19 studies there was a significant positive association
between radon exposure and lung cancer incidence ormortality, in 1 study there was a positive cornlation that
did not reach statistical s g d i i a n c e , in 4 there was no
relation between lung cancer and radon concentration, andin 6 there was an inverse relation. As discussed in Section
lI.B.2, such geographical studies are always dificult tointerpret. This is especially true in the study of diseases
such as lung cancer, for which the major determinant ofrisk is smoking habits and the incidence of which varies
geographically. Another recent paper [S26] examined andreviewed features of 15 of these gecgrapbical studies, allof which are represented in Table 58, and concluded that
their shortcomings rendered them uninformative on thelung cancer risk associated with indoor radon.
The association between radon exposure and the362.
development of lung cancer has been tested much more
directly in case-control and cohort studies, and the resultsof studies available to date are summarized in Table 59.
Early studies, e.g. that of Axelson et al. [MI, relied onsurrogate measurcs of exposure, such as whether houses
were conshuctcd of wood or stone and whether the
residents lived on the p u n d or upper floors. In 10
studies, however, measurements have been made m someor all of the houses. In six of these studies (five in Sweden
i111d one in the United States), a significant increase inlung cancer was associated with increasing exposure after
adjusting for cigarette smoking. In two of them (in Canada
and the United States), an increase in lung cancer wasobserved with increasing exposure, but the result was notstatistically significant. In one (in Sweden) increased
exposure was associated with increased risk for nualdwellers but not for urban, and in two (in China andCanada) there was no i n c a s e in lung cancer risk with
exposure to radon in any catcgory of smokers, despite thefact that the exposure categories varied Gom less than
70 Bq m-3 to 300 Bq m-3 or more. Tbe difliculties of
evaluating studies of domestic radon exposure are dearly
exemplified by the recent publication of two of the largest
and more carefully conducted studies. One, in Sweden[P36], shows a clear-cut association between radon
exposure and lung cancer incidence, but the dher, in
Canada [LlO], finds no such association
Each of the case-control studies has limitations
363.
that hinder interpretation of the results, in addition to the
problems previously mentioned of indirect indications of
exposure and variability in sampling with small numbers.
It might be illustrative to niention a few of the problems.
The study in China was the only one that could reject
statistically a risk estimated by extrapolating results fiom
studies of miners; however, thcre was concern that thehigh indoor air pollution from coal combustion products
might have liiridcred the ability to detrcz an effca ormeasure the cxposure. T l ~ estudy in New Jersey had
mainly extremely low exposures, and the suggested excess
was based on a comparison of only six cases and twocontrols who received exposures greater than 150 Bq ma;
tllus the numbers were too small to provide useful
exposure-response infomiation. The study of women in
Stockholm was difiicult to interpret because adjustment for
subject occupancy (that is, the time a woman actuallyspent in her home) reniovcd the significance of theassociation. The time response, moreover, was inconsistentANNEX A: EPIDEMIOLOGICAL STUDIES OF W I A T I O N CARCINOGENESIS

with the miner studies in so far as more recent exposures
had little effect, and it was the exposures nlany years in
the past, for which the measurements were most uncertain,that had the greatest influence on risk Fuithermore, thelevel of significance of the trend tests was markedly
different depending on whether continuous (actual) or
categorical (grouped) radon concentrations were analysed.
This influence on the choice of trend statistics anddelineation points for grouped analyses points to a lack ofrobustness in the data being analysed. The national
Swedish study is imporiant, but it is somewhat peculiar inthat risk seemed concentrated in men and not in womenand few details were given regarding occupancy and time
response [P36].The Canadian study had generally higher
exposures than the Swedish national survey, but no risk
was evident PlO]. The new study in Missouri was
methodologically sound: exposure measurements weremade close in time to the diagnosis of lung cancer in thew e r 500 cases of lung cancer in non-smoking women andthe spouses served as controls [A18]. Moreover, the factthat the women were not smokers enhanced the probabilityof deteding a radon effect by removing the confusing
influence of cigaretfe smoking. Despite the many -sof this study, an increased risk could not be associatedwith residential radon exposure. On the other hand, anddespite the large number of cases, the data were not strong
enough to predude the possibility that the risk might besimilar to that predicted by extrapolating b m high doses
the risks obtained in studies of miners.
364.
The difference seen in the various studies withregard to the radon effect over categories of cigarettesmoking also point to a lack of robustness in the data
being analysed. Clearly, cigarette smoking was the moststriking cause of lung cancer in these series, with relative
risks almost 14 times as great for persons smoking morethan one pack per day in Stockholm, New Jersey andCanada, and 3 times as great among heavy smokers in
China. In the study in Stockholm, the steepest gradicnt inrisk occurred among those smoking more than 20
cigarettes per day, but there was no comparable dosere&onse &end f i r non-smokers [P30]. 1; the national
Swedish study, radon-associated risks were notsignificantly different for different smoking status. In New
Jersey, an increasing dose-response trend was obsetved insmokers of less than 25 cigarettes per day, no d m response was seen in non-smokers and there was a negative dose-response trend in the heaviest smokers [S51].

365.

It is planned to address the inconsistencies seen
in indoor studies and to provide niore precise informationon the level of risk possibly attributable to residential
exposures by conducting pooled or combined analyses ofthe many series that are being conducted throughout theworld [S73) The fmt attempt to pool similar studies wasrecently made PI.A combined analysis of the studies in
China, Stockholnl and New Jersey revealed no evidence
for a radon-related risk, despite the availability of nearly

81

1,000 lung cancer cases. It was concluded that the lack ofconsistency within and across studies for a radon effedoverall and within smoking categories severely limited theinferences that could be made regarding dre risk related toresidential radon Interestingly, the combined data, whichshowed no association between lung cancer and radon
exposure, were not inconsistent in a statistical sense withextrapolations based on investigations of undergroundminers. Because of the wide confidence limits about therisk estimates for low exposure categories in indoor
studies, it cannot be excluded that the level of lung cancer
risk from indoor radon may be less than the level
predicted from studies of miners. Thus,tbe combining of
the more than 15 studies conducted with general1y similar
methodologies will help to resolve the inconsistencies thatcurrently exist

366.

Since the publication of the report of the BEIR

IV Committee [C6],two major studies of radon-exposedminers have been carried out, providing much additional
data [T3,XI]. In addition, a detailed analysis of 11 minerstudies involving almost 2700 lung cancer cases has been
published [L21]. These studies and the comprehensive
analysis strongly support the BEIR IV Committee's
conclusions that the excess risk of lung cancer following
radon exposure is concentrated 5-14 years following
exposure and that the excess relative risk of lung cancer
per unit exposure decreases with attained age.

367.
There is now considerable evidence that risk oflung cancer bom radon exposure depends inversely on
exposure rate (or on duration of exposure) at high exposure levels. In any case, to make estimates of the risk ofradon-induced lung cancer applicable to modern ompational or domestic exposures, they should be based on
those studies in which exposures and work history data areas complete as passible and the exposures arc at lower-.-rd 0.

368.
In two recent large studies of miners [T3, X l ]estiniatcs of the risk of lung cancer following radon
exposure were substantially reduced when adjustment wasmade for the effect of exposure to arsenic-containing
dusts. The possible role of arsenic in causing lung cancer
in radorlexposed miners has reccived little attention up to
now and requires further evaluation, as does concomitant
exposure to other mine contaminants that might i d u e n mlung cancer induction.
369.
There is now strong evidence to suggest that thejoint effect of exposure to radon and tobacco sinoke on
the subsequent relative risk of lung cancer is less thanmultiplicative, as was assumed by the BEIR IV Committee[C6],
although it seems likely that it is more than additive.
These Tmdings imply that estimates based on h e BEIR IV
Committee's model will underestimate the rkks for

UNSCEAR 1994 REPORT

82

non-smokers and overestimate the risks for smokers. It is
recommended that all the available data relating to these
two issues should be further analysed so that firm
conclusions can be drawn
There is little direct evidence on the risks of lung370.
cancer resulting from residential exposure to radon.
Statistically weak studies are generating c d i c t i n g results.
For the time being, risk estimates should continue to be

based on the studies of occupational exposures, although
without adjustment these are likely to overestimate risks inthe domestic environment. They cannot be based on geop p h i c a l studies, which are always difficult to interpretand which in this case give inconsistent results However,the substantial number of case-conh91 and cohort studies
that are under way might provide useful information.
There is no consistent evidence that radon causes cancer
in tissues otber than the lung.

IV. OTHER RELEVANT STUDIES OF CARCINOGENIC EFFECTS
In the last 15 years a number of studies have371.
been canied out of individuals living near nuclear installations and of participants in atmospheric nuclear tests.
Some of these have recorded unexpected associations
between exposure to radiation and a subsequent increasein the incidence of or mortality from cancer in either the
exposed persons or their offspring. In addition, persons
suffering h n i certain types of hereditary disease havebeen identified as being highly sensitive to radiation, andthere is some evidence that there may be other subgroupsof the population who are not overtly affeaed by suchdkcases but who may also be especially sensitive to theeffects of radiation.

A. CWCERNFiARNUCLE4R

INSTALLATIONS
372
Several studies have reported increased incidenceor mortality rates for leukaemia and non-Hodgkin's
lymphoma in young p p l e living near nuclear insrallations. The studies caused public concern and led to muchadditional research. The principal findings to date aresummarijrxd below.
First, an excess of leukaemia was reported m373.
young people in the village of Seascale, four miles southof Sellafield, which is the site of the principal nuclear fuelreprocessing plant in the United Kingdom. Operations
involving radioactive materials began at Sellafield in 1950.
The excess was reported in a television programme in
November 1983 and was latcr confirmed by an official
enquiry [B7J The Seascale cluster aught be considered,from one point of view, to be suspect it was theoccumnce of the cases that determined both the geographic boundary and the age definition of the cluster.
Television reporters first went to SelIafield, not Seascale,seeking excesses of cancer among adult workers, notleukaeniia among young people in the general population[M6]. One of the investigations that had been recornmended in the report of the enquiry subsequently demonstrated that by July 1986 there had been fwe deaths hrn

leukaemia in the slightly more than 1,000 children born tomotliers resident in Seascale in the years 195G1983
cornpared wit11 an expected number, based on national
The results arerates over the same period, of 0.53 [GI].
summarized in Table 60. Four of the five death were inchildren of age 0-4 years. In contrast, there were no deathsb m Icukaemia and lymphoma ampared with 0.83 expedcd
over the same period in some 1,500children who moved
into the area at some time after their birth [G2].Althoughless marked. the contrast extended to otber fatal cancers
and also to non-fatal cancers for the limited time-period
1971-1984, when expected numbers of non-fatal cancers
could be derived from the national caner register, as isshown in Table 60. Two of the six other cancers were
aon-Hodgkin's lymphoma. At young ages non-Hodglun's
lymphomas consist of a variety of conditions, one of themast common of which is distinguished from acxlte
ly~~iphocytic
leukaenlia only arbitrarily by the number oflyniphobiasts in the blood, and for the study of aetiology
such cases may bettcr be classed with leukaemia thantreated as a sepantc disease. When all cases of leukaemia
and non-Hodgkin's lyrnphoma were studied that
occurred in young people resident in Seascale in theslightly longer period 1950-1988, the cluster in
Seascale was found not to be limited to children who
had been born there [K27]. Eleven cases werediagnosed in this period, and statistically significant
excesses were found in young people not born in
Scascale as well as in those who were born there, therisks being increased by a factor of approximately 10
in each case (9.9 for those not born in Seascale and10.2 for those who were).
374.
Estin~atcsof the average annual dose in the redmarrow that one-year-old children living in Seascale arethought likely to have received from Sellafield discharges
are given in Table 61. Bcforc 1%0, the estimated doses
from Sellafield exceeded those estimated from naturalradiation by about 20%,but aftcnvards tbcy were much
lower. Doses of this magnitude would not be expected tocause the observed nincfold increase in fatal leukaemia in
Ihc children of mothers resident in Seascale.

ANNEX A: EPIDEMIOLOGICAL SWIIIES OF RADIATION CARCINOGENESIS

375.
Furtber study of the affected young people
resident in Seascale and of those bom and resident inWest Cumbria Health District, in which Sellafield issituated, has given potentially conflicting results. In m e
study [G21] comparisons were made between the characteristics of young people born in the West Cumbria HealthDistrict who developed leukaemia, Hodgkin's disease or
non-Hodgkin's lymphoma while still resident in the district
and the characteristics of the up to 16 times more
numerous young people born in the district, resident in it
and registered in the same birth registers as the affectedyoung people, half of whom were also matched forparental residence in the same civil parish. The results
gave no reason to think that the affected young people had
had any more exposure to radioactive contaminants in thegeneral environment than their controls, as evidenced bysuch factors as the bequency of playing on the beach or
eating fish. However, they did suggest that the fathers
were more likely to have been employed at Sellafield (RR= 282; 95% CI. 1.07-7.40) and to have been exposed torelatively large doses of external radiation, particularly inthe six months prior to the conception of the children, as
is shown m Table 62 Other findings (some of which were
statistically sgdicant) include two that would have been
expected from previous observations - namely, an
increased relative risk with a history of maternal exposure
to abdominal radiography during pregnancy and withmaternal age - and some evidence that several other typesof paternal employment might also be associated with anincrease of risk None, however, suggested as large anincrease as relatively heavy paternal irradiation, and noother hctor secmed capable of accounting for the excess
leukaemias. In a later study [Kn] it was shown thatparental exposure before the child's conception could notalone account for the Seascale cluster. The results are
summarized in Table 63. They show that the cluster was
not limited to young people whose fathers rcceived
substantial doses of radiation at work. The one boy withacute lympbocytic leukacmia was not born in Seascale andhis father fell into the second lowest dose category in the
Table (0.01-49.9 mSv), having received only 5.5 mSv.
This boy and the four young people whose hthers had notbeen exposed would alone have caused a significant
excess in Seascale (RR = 4.5; p c 0.01). It may also be
noted that most of the paternal doses wen: received
outside Sellafield F37]. Another study of the influenre ofparental exposure examined the data already collected in
the Oxford survey and found no association between
leukaemia incidence or the incidence of all cancers andexternal exposure of fathers [S34]. In a recent commentary[DB]it is concluded that the hypothesis that preconcep
tion paternal radiation exposure is associated withleukaemia in children is not supported by known radiation
genetics, or by the body of knowledge about the hereditability of childhood leukaemia or by what is known about
radiation and leukaemia risks in other studies. The authors
conclude that the association between paternal irradiationand leukaemia is likely to be a chance finding.

83

376.
Shortly after the Seascale duster was discovered,another cluster was reported near Dounrcay p 4 ] . The
results are less impressive, as a highly significant excess
is obtained only by concentrating on an arbitrarily d e h e dperiod and a geographic area that bisects the l o a l m b ncentre of Thurso (5 cases against 0 5 expecttd within
125 krn of Dounreay in the period 1979-1984). Extending
the time back 10 years (to 1%8) and the distance to
25 kilometres, increases the expected number of cases by
25 and the observed number by only 1. Nevertbelw,
Dounreay has the only other plant in the United Kingdom
where nuclear fuel is reprocessed, makmg the excess dif3icult to dismiss. The excess, however, is equally, if not
more difficult, to attribute to nuclear waste fion Dounreay
itself and to waste arriving near Dounreay by coastal
current h m Sellafield, as the estimated annual radiation
dosc to the bone marrow from low-LET radiation h mthese sources is substantially less than the maximum
annual dose received from fallout natio~llyfollowing theainlospheric testing of nuclear weapons that took place in!he early 1960s, with the estimated annual bone marrowdose from high-IJ3 radiation being no more than the
maximum received from fallout Further studies in the
Dounreay area included a case-control study P I 3 1 and afollow-up study of two cohorts of children, one oC which
included those born to local mothers (birth cohort) and theother of which induded those who moved to the area after
birth and attended school in the area (schools cohort)
18401. The case-control study found that the higher
incidence of childhood leukaemia could not be explainedby paternal occupation at Dounreay or by paternal
exposure to external ionizing radiation before conception.
There was, however, an association with the use ofheaches within 25 k m of Dounreay. The follow-up study
found a non-significantly higher incidence of cbildhood
leukaemia in the birth cohort and a significantly higher
incidence in the schools cohort, suggesting that place ofbirth was not a more important hctor than place ofresidence in the aetiology of childhood leukaemia in the
Dounreay area. One possible explanation of this excess isthat it is caused by population mixing linked to the oil
industry in this otherwise rural area of northern Scotland[K17]. Another report p]did not find any association
between the preconception exposure of fathers andleukaemia dusters in Scotland or North Cumbria.
377.
The next finding to be reported was an excess ofchildhood leukaemia near one of three nuclear sites thatare close to one another in the south of England [R18].
Exposures due to radioactive discharges bum the sites are
estimated to he minimal. The observations are summarized
UI Table 64. Made over a period of 14 years, they suggestthat there might have been an exress of some 37% inchildren under 15 years of age living within 15 km of oneof three negbbouring sites, and because the population of
the area was substantial, this amounts to about 20 cases inall. The greatest excess occurred in children under h e
years of age living within 5 kni of onc or other of the

84

UNSCEAR 1993 REPORT

sites, of which there were 9 cases, giving an excess of
134%. The excess was not limited to leukaemia but wasalso observed with other typcs of childhood cancer, with30 cases of cancer other than leukaemia occurring inchildren under 5 years of age who were resident in wards
less than 10 km fiom the sitrs, compared with 19.4
expected [C30]. A further case-control study of children
aged 0-4 years with leukaemia or non-Hodgkin's
lymphoma established that the above-average rates ofleukaemia in the area could not be accounted for byparental employment in the nudear industry [R24].

378
Several other smaller clusters of leukaemia havebeen reported near other installations in the United
Kingdom, and another cluster of four cases against 0.5
expected has bcen observed in the north ward ofEgremont, a small town 7 km north of Sellafield [Cll].
However, it is unclear to what extent some of theseclusters represent a selection of high rates that occur bychance and a neglect of low rates. To a s c x s thesignificance of these excesses it is neclwary to have adetailed and uniform account of the distribution of allcases throughout the country. So far, this can be provided
only for mortality in the 402 county districts in Englandand Wales for 1%9-1978 [q.
After adjustment for
urban-rural status, population size, social class and healthregion and compared with all the other county distrids,
there was a 15% increase in mortality from leukaemia of
all types @ = 0.01), a 21% increase in ~nortalityfrom
lymphoid leukaemia @ = 0.01) and a 25% increase in themortality from Hodgkin's disease @ = 0.05) in young
people under 25 years of age in county districts with morethan 0.1% of their population living within 16 la of oneof the 15 principal nuclear installations in the country. No
excess of any other cancer, nor of all malignancies
combined, nor of seven groups of malignancies in adults
was found.
379.
An excess of lymphoid leukaemia of about 21%
in these specified districts corresponds to about eightexcess deaths per year. The extent to which the risk ofleukaemia is related to paternal employment in the nuclear
industry is unknown It did not, however, account for theexcess found in the small town north of Sellafield, as noneof the fatliers of the four young people who developed
leukaernia while resident in the area had been irradiatedoccupationally before the child's conception, despite thefact that many Sellafield workers lived in the north
Egremont ward and had received a collective dose thatwas greater than that received by the workers who lived
in Seascale. The overall results of the study do not support
the idea that the excess is due to environmental
No trend in relative risk
contamination by radiation [U].
was observed with increasing proximity to an installation,
as measured by the trend from districts with a low
proportion of their population within 16 km of theinstallation (RR = 1.18) through districts with 100/0-65%
of their population within 16 km (RR = 1.29) to districts

with 66% or more of their population within 16 km(RR = 1.16). The excess relative risks between the districts
around Sellafield and those around the other installations
differed by a hctor of 5 (RR = 1.94 and 1.20), manytimes more than the difference between the estimatedannual doses from Sellafield received by children living in
the vicinity and thc doses estimated for children living
near the other nuclear installations [S16].
380.
Furlher support for the idea that the excess
lymphoid leukaemia seen near nuclear installations otherthan Sellafield is not caused by environmental radiation
comes from a second study using the same data thatexamined mortality around "potential" nuclear installations[C18]. Six sites that had been seriously considered fornuclear installations but where no installation was built
were included, as were two further sites where nuclear
power stations were built but that did not start operating
until aftcr the period for which mortality data wereavailable. After adjustment for the same factors as in theoriginal study, mortality patterns were very similar to thosefound near the existing installations. The relative risks ofmortality from leukaemia of all types and from Hodgkin's
disease at ages 0-24 years were 1.14 and 150,
respectively. The total population near the 8 potential
installations was considerably smaller than that near the 15
existing installations; as a result, the number of leukaemia
deaths was much smaller and the increase in mortality did
not reach statistical significance. However, the increase in
Hodgkh's disease did @ < 0.05).

381.
Reports of small clusters of childhood leukaemia
around nuclear installations in the United Kingdom in the
1980s prompted several large-scale systematic surveys. In
the United Kingdom, lymphoid leukaemia among persons
under 25 ycars old was found to be generally increased in
populations living near nuclear fUel repnxlessing or
weapons produdion facilities but not in those near plantsthat generated electrical energy [C19, FlO]. Mortality from
Hodgkin's disease at ages 0-24 years was also increased,
whereas niortality from lymphoid leukaemia at ages 25-64
years was significantly reduced. Overall there was no
general increase in cancer death in the vicinity of these
nuclear facilities.
382
Lcukaemia in children has also been studied in
the vicinity of nuclear installations in France, the UnitedStates (studies near the Three Mile Island plant and of thecountry as a whole), Canada axid the former Federal
Republic of Germany [CX,H33, H39, H42, J4, M35,
M44, M46, VlO]. The results from France and the UnitedStates provide no evidence that any excesses similar to
those in the United Kmgdom have occurred. The negative
evidence from France is impressive, as tbe communes near
nuclear installations experienced slight (statistically nonsignificant) deficiencies of leukaemia in comparison withboth national rates and the rates observed in control
comn~unesin the same departments, at all ages under 25

ANNEX A: EPIDEMIOLOGICAL m I E S OF RADIATION CARCINOGENESIS
years and at ages 0-4 years, and at distances up to 10 km

and 21 km h m the installations [H39, VlO]. The UnitedStates study 1541 examined cancer rates in counties andcould, therefore, have missed very localiirrd excesses suchas that in Seascale. However, this study was otherwise
large and very complete. Over 900,000 cancer deaths in
113 counties in the United States containing or adjacent to
62 nuclear hcilities were compared to 1,800,000 cancer
deaths in control counties with similar population andsocioeconomic characteristics [J4]. Overall, and forspecific groups of nuclear installations, there was noevidence that mortality for any cancer, induding childhood
leukaemia, was higher in counties with nuclear reactors
than in control counties. For childhood leukaemia, therelative risk in the counties with nuclear reactors,
compared with their controls was 1.03 after plant start-up
and 1.08 before start-up. For all leukaemia, the relative
risks were 0.98 after start-up and 1.02 before.
383.
The first Canadian study [C26, M35] examinedcancer incidence and mortality rates in Ontario in children
born within a 25 lan radius of a nuclear installation andcompared them with the values expected on the basis ofprovincial rates. No signifnnt increases were found The
second study w 4 4 ] used a case-conbol design. The caseseries consisted of 112 children aged 0-14 years who diedb m or who were diagnosed with leukaemia in 1950-1988
and were born to mothers who, at the time of their child'sbhth, lived near an operating nuclear facility in Ontario.
Eight controls per case, matched on date of birth andmother's residence at the time of birth, were identified
h m birth certificates. Data on occupational radiation
exposure were obtained by a computerizad record linkage
with the Canadian National Dose Registry and subsequentexamination of employers' records. It was concluded that
there was no association between childhood leukaenlia andthe occupational exposure of fathers to ionizing radiation
before conception as a consequence of employment in the
nuclear indusby in Ontario. No association was detected
for external whole-body dose, tritium dose or radon
exposures. Odds ratios were close to 1.0 for all radiationdose categories and occupations except for uranium
mining, which had a larger, but not statistically significant,odds ratio.
384.
The study based on the registry of childhood
malignancies in the former Federal Republic of Germany
induded 1,610 cases diagnosed at ages under 15 from1980 to 1990. The design was based on that of the firstsystematic British study FlO] and included allcommunities at least one third of whose areas fell within
15 km of the 18 nuclear power plants and 2 research
reactors that started operation between 1960 and 1988. For
each nuclear installation a nearby control region was
selected with similar regional structure and population
density and whose cancer patients would have attended thesame pediatric oncology centre. The relative risk
compared with the control areas was 0.97 for all

85

malignancies (95% CI: 0.81-1.60) and 1.06 for acuteleukaemia (95% CI: 0.88-1.28) in all regions within a
15 kni radius of a nuclear installation. Increased relative
risks were, however, seen in the subgroup of acuteleukaemia before 5 years of age, especially in areas lessthan 5 km from the installations (RR = 3.01; 95% CI:
1.25-10.31) and for lymphomas (RR = 1.67; 95% CI:
1.07-276)
However, leukaemia incidence in thecontrol areas was unusually low compared with national
rates. As in the United Kingdom, a cmmparable and evenmore pronounced increase was observed in regions where
nuclear power plan& had been projected.

m#].

385.

None of the increases in leukaemia and nonHodgkm's lymphoma reported in the vicinity of nuclear
installations scems likely to have been caused byenvironmental exposure to discharged radioactive
materials, nor can any of them be amunted for bypaternal exposure to radiation at work before the affectedyoung people were conceived. While Gardner et al. [G21]thought that the association they observed between
parental irradiation and the subsequent development ofleukaemia and non-Hodgkin's lymphoma in ofkpring born
and living in West Cumbria suggested causation, theincreases seen in a segment of the West Cumbrian
population arc irnplausible quantitatively when comparedwith existing experimental evidence, as is shown in the
UNSCEAR 1993 Report, Annex G [Ul]. No similar
associations were observed in the children of the survivorsof the atomic bombings in Japan p 3 , Y 4 Y5] or in anyof tbe other studies cited above, such as in Scotland. One
possibility is that the observations relating to parental
inadiation in West Cumbria are amiutable to chance[D28]. Another passible explanation is that the excesses
are due to the spread of infedion resulting from themixing of populations From urban and rural areas [K4,K14, K l q .

a P-UTICIPANTS INATMOSPHERICNUCLE4R WEAPONS TESrS
The issue of cancer incidence in participants in386.
nuclear tests came to public attention wben, at the instigation of one of the pamcipants who had developed
leukaemia, the United States Centre for Disease Control
undertook a study of the mortality of men who had participated in the tcst Smoky in Nevada in 1957. The results
showed that in 1957-1979, 10 men had developed leukaemia (including the index case that prompted thc investigation) in comparison with 4.0 that would have been expectedon the basis of the United States national rates wer thesame period of observation, a difference that was statistically significant @ = 0.008, two-sided test) [Cl, C2].The
data from the Smoky test were analysed in more detail aspart of a later study of participants in a scries of five
weapons tests [R2)In the study it was found that while
the mean recorded doscs for all participants was 0.009 Sv,

86

UNSCEAR 1994 REPORT

leukaemia deaths among Smoky participants tended tooccur among those with higher doses or those exposed in
unusual ways that might have led to additional unrecordedinternal doses from the ingestion or inhalation ofradionuclides. No excess of leukaemia deaths (46 absented
versus 52 expeded) was seen in the complete analysis nor
in any group other than the Smoky participants. The study
also found no evidencc of either a general excess ofcancer or excess risks for any specific sites in the fullstudy population. The only other significant finding
occurred in the analysis of genital cancers among
participants in the Redwing series of tests camed out at
Bikini and Enewitok atolls in 1956 (16 cases obsenfed
compared with 8 3 5 expected; p = 0.02, mesided). This
increase was largely made up of prostate cancers (11cases). It could be tbe kind of chance fmding that must be
expected when many dEerent rates are compared in asmgle cohort (see paragraph 31). Prostate cancer has notbeen associated with exposure to highdose-rate, low-LET
radiation in the studies of survivors of the atomic
bombings or studies of external medical radiation.
Although sgnificant increases of prostate cancer have beenreported in employees of the United Kingdom Atomic
Energy Authority (I341 who were monitored for various
radionuclides including tritium, it was not found in
employees of the United Kingdom Atomic Weapons
Establishment [B5] nor has it been seen in radiation
workers in general. Further follow-up of the Atomic
Energy Authority employees [ F l l ] revealed that theelevated mortality was limited to employees UI a slngle
plant. A case-control study found the increase was limited
to nien who worked in environments contaminated bytritium and other radionuclides [R25].Whether this is achance finding hom the examination of multiple
subgroups or the effect of a particular radionuclide cannot
be determined from the present data.
387.
The United States data have been criticized on
two grounds. Fit,the comparison with national rates isinappropriate [Cl, C2,R2]. Seandly, the comparison
within the series of tests that included the test Smoky
shows that mortality from all cancers increased with thes h e of the recorded dose [B14], whereas when all fiveseries are combined, the difference in rates between tbe
high- and low-dose groups is trivial. This is to be
expected, as the recorded doses were much too small forany detectable effects to be seen on the basis of the recent
results from the survivors of the atomic bombings inJapan The mean rccorded gamma dose was 9 mSv, andonly 1.7% of the participants had dabes in excess of
50 mSv. Among the Smoky participants the deaths fromleukaemia tended to occur in persons with higher rccorded
doses: 6 of the 10 leukaemia deaths occurred in participants with at least 0.03 Sv recorded dose,compared with
only 1.34 expected @ = 0.03). It is, bowever, notable that
4 of the 10 leukaemia deaths in the Smoky participants
occurred in a group of 730 men in the task forces Waniorand Big Bang (constituting 21% of the total number of

Smoky participants), who were exposed in unusual ways,
including witnessing a shot from trenches within 3 km of
ground zero and carrying out exercises in areas
contaminated by recent previous tests. It is not impossiblethat these men received substantial additional ulvecorded
doses internally born the ingestion and inhalation ofradionuclides. One of the leukaemia cases may haveresulted from radiotherapy for another malignancy.
As a result of the findings in participants in the388.
Smoky test and of the concern expressed by participantsin the British tests, the United Kingdom Ministry of
Defence commissioned an investigation of the health ofparticipants in the programme associated with the British
tests that were camed out in Australia and on islands in
the Pacific between 1952 and 1958 [D3, D4].The study
included 21,000 men who were identified in the records ofthe Ministry of Defence as having participated in the
programme and also a control group of similar size, madeup of men of the same ages, same services, same
proportion of officers and same date of entry to the study
who did not participate in the programme but who had
served in tropical or subtropical areas while the tests werebeing conducted. The results showed that not only weretile total niortality and the niortality from all neoplasms
combined almost identical in both groups but tbey werealso substantially less than the rates apwkd on the basisof the corresponding mortality rates inEngland and Wales.
In a later study of the same populations with longer
follow-up [D24], statistically significant differences
between the participant and control group were W e dfor 4 of the 27 cancers examined. In two instances theniortality was higher in the participants (leukacmia, 1.75
titnes higher, bladder cancer, 2 6 9 times higher) and in
two instances the mortality was lower in the participants(cancer of the mouth, tongue and oesophagus, 0.45 times
that in the controls; lung cancer, 0.85 times that in thecontrols). In no case was the mortality in the participantssignificantly greater than would have been expected bom
the national niortality rates (standardized moilality ratio forleukaemia of 1.00 and for Madder cancxr of 1.04), thesignificant excess in the participants being due in eachcase to an unusllally low niortality in the controls. With
the statistical test used, some statistically significant
differences were to be expected by chance alone when 27
different diseases were examined, and it was concluded
that all of the findings are likely to have been due tochance. A sniall, statistically non-significant excess ofleukaenlia in the Grst 25 years after participation could not
be ruled out (standardized mortality ratio of 1.23, based onU) deaths), but it could not be aMibuted to any known
cause, as it was 1101 concentrated in men known to havebeen exposed to radiation or men involved in any
particular operation or eniployed in any particular job.

In a separate study of New Zealand participants389.
in the British ahnospheric nuclear weapons tests hl
1957-1958, 528 men knavn to have participated in the

ANNEX A: EPIDEMlOLOGlCAL STUDIES OF KADIATION CARCINOGENESIS

tests and a control group of 1,504 men who were in theRoyal New Zealand Navy during the same period but who
did not participate in the tests were follawed until 1987 forboth mortality and cancer incidence [PZ']. Mortality fromcauses of death otber than cancer and mortality and cancer
incidence born cancers other than haematologicalmalignancies were similar among test participants andcontrols. There were seven deaths from haematologicalmalignancies among test participants (RR = 3.25; 90% CI:
1.12-9.64; p = 0.02), including four from leukaemia (RR= 558; 90% CI: 1.04-41.6; p = 0.03) For haematdogicalcancers the relative risk was 1.94 (90% CI: 0.744.84;
p = 0.10) and for leukaemia it was 5.51 (90% CI:
1.03-41.1; p = 0.03) However, as noted by the authors,
one of the four leukaemia cases was diagnosed as chronic
lymphocytic leukaemia, and the temporal distribution of
the cases, one within 15 years of exposure and three morethan 25 years after exposure, makes it unlikely that thecases resulted fiom radiation exposure 6om the tests.
Interpretation of these three sets of results from of390.
participants in nuclear weapons tests is a matter of some
controversy (see, e.g. [B14, J7j) The results arc not clearcut however, taken together, they provide no evidence fora greater risk of leukaemia in exposed participants than in
unexposed individuals or for a greater risk than expeaed
fiom other sources, such as the atomic bombings.

C. SENSITlVE SUBGROUPSOF THE POPULATION
It has long been known that patients with certain
391.
hereditary diseases have an increased sensitivity to radiation. As an example, patients with ataxia-telangiectasiaare
at increased risk of developing certain cancers and often
develop devastating necrosis of normal h u e when given
therapeutic irradiation [S43]. Retinoblastoma patients withthe rb gene are at increased risk of subsequently develop
ing a wide variety of other turnours, and when treated withradiation they appear to have a higher excess absolute riskof second cancers than patients irradiated for the nongenetic form of the disease p12, EA].
The increased radiosensitivity associated with392
hereditary diseases such as those mentioned above is notnecessarily confined to persons in whom the genetic
disease is manifest Again, it has been suggested by way
of example that ataxia-telangiectasia heterozygotes may
have an increased risk of developing cancer. Swift et al.
[S43] ascertained rempeaive cancer incidence rates in
110 families of ataxia-telangiectasiapatients in the UnitedStates. Among the adult blood relatives of the affcdcd
patients, a total of 138 cancer cases were ascertained
compared with 103 expected based on cancer incidence
rates for Connecticut among spouse controls who were
not consanguineous with the affected patients, 32 cancers
were found compared with 40.9 expected. Using a81

maximum-likelihood method that accounts for eachrelative's prior probability of heterozygosity, it wasestimated that for men who are heterozygous for ataxiatelangiedasia the relative risk of all sites and types ofcancer combined was 2 3 @ = 0.014). while for women itwas 3.1 @ = 0.004). Among the blood relatives ofaffected patients, the commonest cancer was breast cancer,
with 27 cases &served ampared with 205 expectedbased on Connecticut cancer incidence rates, while forspouse controls there were 3 obse~~ed
compared with 7.2
expected. These data led to an estimated heterozygote
relative risk for breast cancer of 6.8 @ = 0.006).
In a M e r prospective study of 161 families
393.
affected by ataxia-telangiedasia, Swift et al. [S59]compared cancer incidence and mortality in 1,599 adultblood relatives of patients with ataxia-telangiectasia and821 of their spouses, who served as controls. This stlady
included many of tbe same families as tbe previous study,
but the periods of follow-up in the two studies did not
overlap; in the later study the individuals were followed
prospectively for a mean of 6.4 years. Cancer rates weresignificantly hlgher in the group of blood relatives than in
the spouses, specifically in the subgroup of 294 blood
relatives who were known to be heterozygous for theataxia-telangiectasia gene. The estimated relative risk ofcancer of all types among obligate heterozygotes ascompared with non-carriers was 3.9 @ < 0.005) in men
and 2 7 @ < 0.005) in women, and that of breast cancer
in women was 3.8 (no significance level given).

In a case-control substudy, documented occu394.
pational and fluoroscopic diagnostic exposures to radiationin the 19 female blood relatives in whom breast cancer
was diagnosed during the period of prospective
observation were compared with exposures for 57 matchedblood relatives who did not have breast cancer. Among theblood relatives, women with breast cancer were more
likely than controls without cancer to have been exposed
to selected sources of ionizing radiation (RR = 5.8;
p = 0.005), suggesting that at least part of the observed
e x m of breast cancer may be due to an harased
susceptibility to ionizing radiation. These findings,
however, have not been confirmed and were the subject ofconsiderable debate (see [S59D. It appears thatfluomscopic procedures that contributed negligible breast
exposures, such as barium enemas, were consideredmeaningful; the age distributions of breast m c e r cases
and their controls were significantly different, with thecontrols being much younger and less likely to develop
breast cancer; and when general population rates wereused to compute expected number of breast cancers
among the ataxia-telangiedasia hetemygous women, theexcess risk and the level of significance were no longer
striking.
The studies of Swifi et al. are the largest to date395.
of cancer among the relatives of ataxia-telangiedasia

88

UNSCEAR 1994 KEPORT

patients. A smaller study of the families of 67 patients in
the United Kingdom found that three parents of affeded
patients had died of cancer F2]. Two of the deaths were
fiom breast cancer compared with only 0.17 e x p e abased on mortality rates in England and Wales, and tbe
excess was statistically significant @ < 0.05). However, no
excess mortality was found among the grandparents of theaffected patients. The interpretation of these studies mustremain at present uncertain. More studies of the relativesof affected patients comparable in size to that of Swift etal. and a method of identifying ataxia-telangiectasiaheterozygotes in the general population would be very useful toclarify the situation. The frequency of ataxia-telangiectasia
heterozygotes in the population is estimated to be between
1% and 8% [S43]. If the fmding of an increased tendency
for them to develop cancer is confirmed it would be ofmajor significance, whether or not it is caused by anincreased radiosensitivity. For further discussion of this
topic, see Annex E in the UNSCEAR 1993 Report PI].
3%.
There are a nunibcr of genetic conditions forwhich radiation has enhanced the development of s e m d ary cancers. Children with familiar retinoblastma have adeletion in chromosome 13 that prcdispclses to ostw
sarcoma. and radiation appears to cause a second mutationin an osteoblast that leads to a high rate of osteosarcoma

development Further, these children are at a significantly
increased risk for developing cancers of the COMC&~
tissue and brain and skin melanoma, because radiotherapy
appears to enhance the inborn swceptibility to cancer
development P I . Children treated for medulloMastoma
who have basal cell nevus syndrome develop multiple
basal cell carcinomas in irradiated skin at an exceptionallyhigh rate [S71]. Patients with a rare familial cancer
syndrome called the Li Fraumeni syndrome are atincreased risk for cancer development largely because of
an inheritid mutation in the p53 tumour suppression gene.
Radiation appears to enhance the development of seamdary turnours among patients with this syndrome p 4 ] .
397.
In a new analysis of the breast cancer risk among
atomic bomb survivors, a high excess redative risk associated with radiation dose was apparent for early-onset
breast cancxr, defined as cancer diagnosed before age 35
years [L20]. These early-onset cases occurred almost
exclusively among women exposed before the age of 20
years. The authors suggested that this may be the consequence of a small radiation-susceptible subgroup of
exposed women The authors cautioned that the interpretation of these data needed to be confirmed in studies
from other irradiated populations or in experimental
investigations.

CONCLUSIONS
398.
In recent years a substantial number of new
epidemiological studies of the carcinogenic effects in manof exposure to external low-LET radiation at high dose
rate have been undertaken. Many of these studies are of ahigh quality, and they contribute substantially to the knowledge of the consequences of human expasure to this typeof radiation under these conditions. In addition, many of thestudies that have been under way for several years havebeen extended. The new information is broadening the baseof data on which to evaluate the association between
radiation exposure and cancer inadence or moriality.
399.

The Committee i~cknowledgesthat for the time

being quantitative evaluations must continue to be based
primarily on the findings of the life span study cohort ofsurvivors of the atomic bombings However, as thematerial in this Annex illustrates, some other studies arc
able to provide useful risk estimates for a substantial
number of specific sites. It would be very useful if moreparallel analyses of multiple studies could be made, as wasdone for the radon studies or the studies of cancer of thebreast The Committee recognizes that a limitation of thelife span study is its inability to address directly the effectsof low-dare-rate exposures. Other studies are needed toprovide information on the appropriateness of risk
estimates derived h highdose-rate exposures.

400.
In the UNSCEAR 1988 Report [U2],estimates of the risk of exposure-induced death andloss of life expectancy following exposure to 1 Gy of
low-LET radiation delivered at high dose rate weremade on the basis of estimates of the excess absoluteand excess relative risks, averaged for age at
exposure arid sex, observed in the life span study
cohort of survivors of the atomic bombings in Japan
using data through 1985. These estimates were
calculated on the basis of unweighted organ absorbed
dose. Individuals whose estimated k e m a doses weregreater than 4 Gy were included in the calculation,
and a linear dose-response relation was assunied bothfor leukaeniia and for other sites of cancer. For
leukaemia the risks were assumed to apply from thesecond year following exposure up to 40 years after
exposure, while for otller types of cancers they wereassumed to apply from 10 years after exposure forthe rest of life. It was assumed that there was no
additional variation in the risks with time since
exposure and that risks for men and women were thesame. While age-specific coefficients were used toestimate the total risk of all cancer, for specific sitesof cancer the only estimates that were presented were
those based on risk coefficients that had been
averaged over all ages at exposure.

ANNEX A: IlPIDEMIOLOGICAL STUlIIES OF RADIATION CARCINOGENESIS
401.
Data on the incidence of cancer in the life spanstudy have become available for the first time and may becompared with the mortality data, which have been
extended through 1987 P I . Estimates of the btal risks
associated with exposure to high-dose-rate, low-L43
radiation in this Annex have been based on this extended
life span study mortality data. The analyses of the more
recent data differ from those used to describe the risks inthe earlier life span study data. In particular, excess risks
in the life span study were described using general models
that allowed for differences in age at e x p u r e and sex in
the excess risks. Survivors with shielded kerma estimatesin excess of 4 Gy were excluded, and risks werecomputed in terms of weighted organ doses in which theneutron dose was given a weight of 10 and the gammadose, a weight of 1. Because the time-constant additive(i.e. constant absolute risk) model no longer fits the life
span study data, risk projections based on the constantabsolute risk model are not included in this Annex. The
Committee acknowledges that risk projections must take
into account importantvariations in radiation-induced risks
with sex, age at exposure and time since exposure and that
more efforts are needed to distinguish significant aspectsof the different patterns of risk seen for specific sites h m
the random variability inherent in comparisons of sitespecific risks.
402
The life span study data for solid tumours from1950 to 1987 arc consistent with linearity betwccn 0.2 Sv
and 4 Sv (weighted dose), but they provide little direct
evidence about the shape of the dose response at lower
doses. Risk estimates are presented in this Annex for
doses of both 1 Sv and 0.2 Sv and for a Japanese
population with the demographic characteristics thatprevailed in about 1950. The results for 0.2 Sv show aslightly greater risk proportionally than for 1.0 Sv because
the risk of exposure-induced death is non-linear in dose. A
linear dose-response model does not fit the life span study
leukaemia data, but a linear-quadratic model does. The
data from the life span study (195b1987) lead to a
lifetime risk estimate for solid tumours of 10.9% at 1 Sv;
the estimate for 0.2 Sv is 2 4 % Fable 31). For leukaemia
the corresponding numbers are 1.1% at 1 Sv and
0.14% at 0.2 Sv. For all cancers, solid tumours plus
leukaemia, at 1 Sv the risk is 12.0% and at 0.2 Sv it
is 25%. The corresponding estimate of risk for all
cancers in the UNSCEAR 1988 Report [U2] using a
multiplicative projection was 10.7% at 1 Gy (organabsorbed dose). Projections beyond the follow-up period
for models in which risks were allowed to decrease atlonger projection times lead to lifetime risk estimates 20%
40% lower than 12.0% (Table 31).
403.
No attempt has been made in the above risk
estimates to address the ,issueof dose rate for either solid
tumours or leukaemia. The estimates are presented without
any adjustment for such effects. The application of a small
dose and dose-rate effectiveness faaor was recommended

89

in the UNSCEAR 1993 Report [Ulb Annex F,"Influenceof dose and dose rate on stochastic effeds of radiation". If
a factor such as 2 (as was used by ICRP VlOD is applied,
the above estimates for solid tumours for both 0.2 Sv and1 Sv would be halved. Those for leukaemia would also beapproximately habed for a chronic exposure of 1 Sv as
compared with an acute exposure, while those at 0.2 Sv,
having already been determined by a linear-quadratic
response, would stay the same.
404.
The publication of the life span study incidencedata, available for 19581987, is an important addition to
the body of knowledge on the late effects of radiation. The
strengths of the incidence data include the high quality ofthe diagnostic information and the larger number of cases,
especially for sites such as breast, thyroid and skin, withlower lethality. Their limitations include the absence ofdata on solid cancer incidence for the first 13 years afier
exposure in the Japanese population and the need to adjust
for migration. It is noteworlhy that in the incidence
analyses two cancers, that of the oesophagus and multiple
myeloma, for which statistically significant risks had been
seen in the mortality data, did not exhibit statisticallysignificant risks.

105. Additional information has become available on
the effects of prenatal exposure to radiation since tbc
subject was last reviewed in depth in the UNSCEAR 1986
Report [U3]. The evidence regarding the causal nature of
the increase in childhood cancer following exposure of themother's abdomen to diagnostic x rays in pregnancy is
still equivocal. The best estimate of the excess absoluterisk of developing cancer before age 15 years following
prenatal exposure to x rays at high dose rate is about
5 lo'* G ~ " , similar to the lifetime risk for adults. Thisestimate does not include any cancers induced by prenatal
exposure to radiation that may arise in the age group of 15
years and above. Data from the survivors in utero at thetime of the atomic bombings in Japan initially revealed anincrease in cancers in the ages of 15-39 years, but no newcancers were found in the exposed group in tbc next four
years of follow-up [Yl]. The exms is large but not, sofar, statistically significant.
406. In the UNSCEAR 1988 Report [U2] it was notedthat signifimt excess cancer mortality had been seen for
the first time for some cancers at doses between 0.2 and
0 5 Gy. There is also some limited evidence that directly
points towards the carcinogenicity of doses in the 4 . 2 Gy
range, although each of these studies bas weaknesses. The
studies indude childhood cancer among those exposcd todoses of about 0.01 Gy in urero, for which there is anequivocal but possibly significant increase; both incidence
and mortality for all cancers other than leukaemia in thelife span study cohort, for which, although not significant,there are smooth increases in relative risk with increasing
dose in dose categories in the <0.2 Gy range; and thyroid
cancer in the Israeli tinea capitis study.

90

UNSCEAR 1994 REPORT

Since the publication of the UNSCEAR 1988
407.
Report p 2 ] , a substantial amount of new information has
become available on workers at nuclear plants in the
United Kmgdom and in North America. Tbe studies provide some quantitative information on the effects ofprotxacted low-dose exposures to low-LET radiation.
Although at present the confidence limits are wide, thesignificant value for leukaemia in the study in the United
Kingdom, 0.8% SV-', is similar to values derived from thelife span study. Also similar to the life span study results
is a non-significant value for all solid tumours of about
10% SV-l.Additional data acquired through extensions of
the follow-up and the inclusion of extra cohorts should
increase the information available fiom this study in futureyears. On the other hand, studies of workers m the UnitedStates, which are of somewhat lower power (smaller
population), have found no evidence of an association
between exposure and leukaemia or all cancer.
Data have recently become available on several
408
populations in the southern Urals, including workers with
substantial exposures in a nuclear plant and populations
exposed as a result of environmental releases and a&dents. In the study of workers, only limited information isavailable so far on the methods of data collection, anddetailed internal analyses are only in the process of being
carried out The study could be very informative, however,since the doses were substantial and the workers had
individual dose measurements, good medical supervision
and a good control cohort. It is hoped that the analysis ofthese important worker experiences will be completed andpublished. For the studies of populations exposed tocnvironmerltal releases, it would be desirable to improve
the quality of the dose estimates and the follow-up data.
Initial findings based on the follow-up of the Techa River
cohort suggest elevated risks of leukaemia and solidcancers. While a better understanding of the dosirlietry andthe follow-up is needed, results are broadly similar to
those derived h m atomic bomb survivors for leukaemia.
No studies have yet provided evidence that anincrease in thyroid cancer can be clearly amiuted to 1 3 1 ~However, the relative importance of the various factorsthat might affect these results is not clear. These fsctors
include the low dose rates involved in 13'1 expcsures. thebeta-ray distribution m the gland, the rather limited followup in some studies and biological factors such as the cellkilling, which usually follows treatment with 1311. In
addition, most of tbe evidence concern those exposed in
adult life, and by analogy with recent results for thyroid
cancer following external low-LET radiation, the possibility of substantial risks following childhood exposure lo
1311 remains. Medical e x p u r e s to l3'1 have been associated with i n d risks for some otber sites of cancer,
but the available data do not provide strong evidence of acausal relationship. It should be noted that leukaemia has
not been observed in many thousands of adult patientstreated with 1311. Further studies of the effects of internal409.

exposures to low-LET radiation from 1 3 1and~ other radionuclides would be desirable, especially in children, forwhom there is little information.
410.
Studies of patients who have been injected withor workers who have ingested one or another of thevarious isotopes of radium provide condusive evidence of
the ability of alpha radiation in the skeleton to cause bonetumours. The excess absolute risk does not appear todepend strongly on sex or age at exposure and amounts toabout 5 lo4 SV-* for lifetime. The minimum induction
period appears to be short, no more titan about 3 ears,
and the studies of patients injected with shoxt-lived g4Q
provide clcar evidence that the period of expression of theradiation-induced tuniours lasts no more than about
30 years. Further analyses of the data on the risk of bonetumours in persons exposed to the various isotopes ofradium in terms of the risk per person-year at risk as
related to dose, treatment period, time since exposure andother factors would be helpful in enabling comparisom
with studies of populations exposed to other types ofradiation. In addition to an increase in bone tumours,
excesses of cancers of the breast, liver, paranasal sinuses
and mastoid air cells, and also of multiple myeloma, havebeen reported intient. injected with or workers
contaminated with xRa. Funha study of these inorawr
and the associated dosimetry, including, wbere appropriate,
the role of external gamma-radiation would be
informative.
41 1. There is strong evidence that injected Thorotrast
is a cause of liver cancer. The minimum induction period
is about 10 yean, and relative risks are higher among
those injected at younger ages, although absolute excess
risks do not depend strongly on age at exposure. Risks are
similar in males and females, and the amulative risk ofmalignant liver tumours, although subject to many
uncertainties owing to possible confounding or enhancing
bctors, is estimated to be about 300 lo4 G ~ - ' , or
15 lo4 SV-', quite similar to results from low-LET
cxposure. There is also definite evidence that injectedThorotrast is a cause of leukaemia, especially myeloid
leukaemia and erythroleukaemia, and it seems likely that
it is also a cause of a variety of other cancers. Perhaps
because the dose is highly localized at sites of microscopic
dimensions, risk estimates for leukaemia based on patients
exposed to Thorotrast are much less than would be
expected based on low-LET risks (ie. an RBE of 1 fitsbetter than 20). Nevertheless, additional analyses of therisks of liver cancer and leukaemia in the German,
Japanese and Pomguese studies based on the concept of
person-years at risk would be helpful, as would calculationof the relative risk and corresponding significance levels
for other types of cancer.
Additional studies and many more cases of lung412.
cancer attributable to radon in mines have b m m eavailable for analysis since the publication of the report ofANhTX A: EPlDEMlOLOGICAL STUDllES OF RADIATION CARCINOGENESIS

the BEIR IV Committee [C6].There is some recent
evidence that the excess risk of lung cancer following
occupational exposure to radon may be greater at low
exposure rates than at high exposure rates, but not all
studies show this. Studies of the joint effect of exposure toexternal, predominantly low-LET radiation h m theatomic bombs and to tobacco smoke on the subsequent
relative risk of lung cancer has shown that the two Factors
combine to increase the relative risk in a fashion that ismore than additive but less than multiplicative. There is
now strong suggestive evidence that the joint effect of
exposure to radon and tobacco smoke on the subsequent
relative risk of lung cancer may also be less than multiplicative. Although it may eventually need to be modified
to take these two factors into account, the empirical model
proposed by the BEIR IV Committee [C6] adequately
summarizes the effects of occupational exposure to radon.
Arsenic is a newly recognized confounding factor in someradon exposure circumstances, raising the question whether
exposures to other substances in mine air, such as silica ordiesel exhaust, might also modify risk Studies of cancers
other than those of the lung following radon exposure
provide little evidence of a positive association.
At present there is liule direct evidence on the413.
risks of lung cancer resulting kom residential exposure toradon Although a substantial nunlber of geographicalstudies have been carried out, difficulties in their interpretation render them unsuitable for use in risk estimation
Until results become available of case-control and cohort
studies that are currently under way, estimates of the risksof residential exposure to radon must therefore continue tobe based on the results of studies of the effects ofoccupational exposures.
Following reports of a leukaemia duster ncar the414.
Sellafield reproarsing plant in the United Kingdom,
several other clusters were found in the United Kingdom.
The subsequent study of the potential radiation doses thatrmght have been received from radionuclide releases ator near the sites suggests that the dusters arose either bychance or for reasonc other than radiation exposure. A
tentative explanation based on an association of childhood

91

leukaemia and paternal exposure has largely been discounted following extensive investigations of the SellaGeld
arca and elsewhere and because there is no sound genetic
basis for this effect415.
In future research, several steps could be taken to
facilitate the comparison of risk estimates h m different
epidemiological studies. First, risk estimates per unit doseshould be published. Admittedly this is difficult for manystudies because estimates of dose are unavailable or ofpoor quality. Nonetheless, a u d e estimates of dose for the
exposed population, along with clear statements of thelimitations of those estimates, are essential for a comparison of risk estimates from different studies. Whenestimates of doses to individuals or groups are used in ananalysis, it is useful to describe their uncertainties and toattempt to evaluate the effect of thcse on risk estimates.
Pierce et al. [P31] provide methods for this. Even if
individual doses are not available, investigators should
be cncouraged to use modem regression and modelling
methods [B28, B29, P32, V12] in their analyses ofeffect modification and temporal patterns of risk. Suchmethods are especially useful as an alternative tosubset analyses.
416.
A willingness on the pad of investigators to sharedata that are more comprehensive than the data usuallyoffered in most publications would be another step tohcilitate comparative analyses of available data. For
example, data on su~vivoxsof the atomic bombings inJapan are available from the Radiation Effects Research
Foundation and can be used in comparative analyses ofother radiation-expased populations. Other groups should
be encouraged to make their data available in a likemanner so as to encourage parallel analyses The Committee
also notes the need for more careful, formal examinationof the evidence for similarities or differences in risk
between cancer types The joint analysis metbods suggested
by Pierce and Preston [PU)] should be useful in suchinvestigations. There is, in summary, much scope forenhancing the value of epidemiological studies, making
then1 better able to contribute to the quantification of risks
bom radiation cxpmures.

UNSCMR 1994 REPORT

92

Table 1
Examples or high and low cancer rates In various populalions O[PI 01High cmcer inckkme
Sire of CMCC

Popuiation

Nampbarynx

Low cawer incidence

.k

Rae

Popul&n

Rare

Malcs

1Img Kong
Singapore (Chincae)
United States. Hawaii (Chinese)

28.5
18.1
14.1

German Democratic RepuMic
United Kingdan, Oxtad
Rnlmd

0.3
0.3
0.3

FcmalesIImg Kong
Singapore (Chincre)
United States, Los Angles (Chinese)

11.2
7.4
3.0

United Kingdom, Birmingham
finland
Guman Democratic Republic

0.1
0.1
0.2

Males

Frulcc, G h a d m
Brazil. Pwto Alegrc
Bermuda (black)

26.5
25.9
24.9

Algaia. Selif
Israelhaly, Latina

1.4
1.4
1.8

Fanales

IndiaBmpIalore
China. Tianjin
Brazil, P a t o Alegre

8.8
8.0
6.9

Romania, a u j
Spaiq k a p
Poland, Warsaw (rural)

0.4
0.4
0.4

Malcs

Japaq Yamagata
Portugal, Villa Nova & Gaia
Gxta R i a

93.3
47.8
46.9

India, Ahmedahd
GambiaUnited States. Lor Angdes (Filipino)

21
3.9
4.0

Femaleslapa- Yamagata
United Stales. Lor Angeles (Koran)
E a a d a . Quito

42.9
22.9
22.7

GambiaIndia. Ahrncdahd
Kuwait (Kuwaitis)

1.5
1.5
20

Malcs

I b i l a n Q Khon Kach
Gina. Qidong
Mali. Bunako

90.0
89.9
47.9

Netherlands, Maastricht
IrelandParapay. huncibn

0.8
1.1

Females'Ihailand, Khon Kachaim, O i h g
Mali, Bamako

38.3
245
21.4

France, l d r e
Nuhalands, Eindhovm
United Kingdan. Birmin&am

0.4
0.4
0.6

Males

New &,land (Maori)
United Statu, Sew Orleans (black)
United &n@cm. Scoclmd

119.1
115.9
88.1

Mali, Bamako
Ecuador. Quito
India. Madras

4.8
8.3
8.5

Fcmalcs

Canada, Smthwat Taritoricr m d Y u hUnited States, Hawaii (Hawaiian)
China. 'lianjn

51.8
39.5
33.2

India. Madras
Algcria, Setif
Spaiq Granada

1.4
1.7
25

Bras

Females

United S t a t q S m Francisco Bay Area (white)
United States, Hawaii (Hauaiirn)
Brazil. Porto Alcgrc

104.2
100.2
78.5

GambiaAlgeria. Serif
Gina,Qidong

3.4
6.4
9.5

Orwx

FcmalcaPens Trujillo
Brazil, Goiania
India, Madras

54.6
48.9
47.2

IsraelUnited States, Hawaii (Japanese)
China, Qidong

26
3.6
3.7

o=PhY

StomachLiverhg and bronchus" Numbers i v c n are age-standardized (world) annual incidmec r a t o p a lW,WO population.

1.1

ANNEX A: EPlDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

93

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Populuric~tsrurlial
Snuly

Typc of sftuly
Churacrerivrics

Breast cancer
15~01

Breast cancer
1041

Childhoodcancers
ITS, '1'6, '171

N ~ i o n noriginlFollau-up&curs)

Torul
personyears aType of aposure

Cunccrs sndial

Typc of dosimchy

Case-ccntrd
529 cases
5 3 contrds
frcm a cohcrt
of 56,540 womcn

157 exposed womcn
901 uriexpolicd wonicn
Age: <45->60 (51)Denmark

1247(-16 years
pcr case)n.a.

Radiotherapy

Individual doses f r m
thcrapy rccords andexperimenlal ineasirrenlents

Ccntralateral breast

Case-cmtrd
90 casm
264 cmtrds
f r m a cohortof 82,700 wamcn

110 exposed woriien
244 unexposed womcn
Age: <SO->70 (61)

United Statesc 12(-5 years
per case)

n.8.

Adjuvant radidherapy

Individual doses franthcrapy rccords andcxpcrin~cntalmcnsurcmcnts

Acute non-lymphocytic leukaemia andmydodysplnsia syndrome'

Cnsc-cuntrd
within 9,170m c ~ n k cohatr

112 exposed persuns
388 uncxpoved pcrscms
45% Icmalcs
Agc: 0- I 8 (7)5-40

50,609Mjuvant radidhcrnpy

Individu;~ldoscs lrcm
therapy rccords andexpcrimcntal mcasuremcnts

Thyroid,' lcuknemia, bone rarcomnr''

Cnn:~da. Fri~nce.
Nctherlnnds, Itnly.
United Kingdom.
United States(5.5)

Treal~iicntd bc11ig11disease
Chiidhood skinhaemangiaua[FlZFlS]

Case-cmtrd
within 14,467mcmbcr d o r t

144 expcsed persms g
314 unexposed persons
67% funales
Age: 0-1.5 (0.6)

Sweden

25-64

n.a.

Radiotherapy

Avcrap doses based mexperimental measurementswith agc adjustment

Thyroid..
breastAnkylosing
spondylitis

Mortality

14,106 exposed pctrsons
16.5% femalcs
Age: 20-60

United Kingdom<3->SO

183,749( 13.0)

X-ray thcrapy

Avcrag doscs based on
infaniatica from a
1 in 15 sample

Leulracmia,' olhcr neoplasms (cxccpt

Incidence lmortality

10,834 exposed persons
16,226 unexposed persons
50% females
Age: <1-15 (7.1)

Israel26-38

686,210(25.3)

X-ray-induced epilation

Individual doses franphantom measurcmenls
based on institution and age

Inadeoce: thyroid.. sIin,* brain,'salivary $sod.* breast
Mortality: head and n-'leukaemia

Ncw York tinea
capitis[Al, S8, S61]

lncidcncc

2,226 exposed pasms
1,387 unexposed pcrsms
16.1% females
Age: 1-19 (7.7)

Unilnl Statcs

20-39

98,881

X-ray-induced cpilation

Kcprescntativc doscs b s c d
on standard trcatrncnt

Thyroid,' skin,' brain, Icukacmia,
salivary gland

New York acutepost-paiturnmastitis

lncidmcc

571 cxposcd women
993 unexposed womrm
Age: 14->40 (27.8)

United States

X-ray therapy

Individual doses franthcrapy refords

Breast'[MI
Xnea capitis
F120, R5,
R10, R15j

1~91.

(25.4)

20-35

38,784(25.1)

brain;

bone and soR tissue.

colon)*

Table 2 (continued)

Poptrl(~rim~
studiedStudy

Type of study
C/turucieristics

N a i o n d origin

Follow-ty,

Dews)

Total
person,,Type of orposwe

Cancers studied

Type of dosimcby

0

Rochester thymicirr;~di:~tion[H2Z S10]

lncidencc

2,652 exposed pmsoos
4,823 uncxposrd persons
42% females
Age: 0-1

United States

23->50220,777(29.5)

X-ray thcrapy

Individual doses fromthcrapy rccords

Thyroid,'

Swedish hcnign
breast diseaseinadcnce

1,216 exposed women
1,874 unexposed wo~iicn
A p : 10->85

Sweden560

56,900(18)

X-ray therapy

Individual doses fromtherapy records andphantom measurements

Breast*Mortality

2,067 exposed womcn
Agc: 35-60

United Kngdoni

5->30

53,144

X-ray therapy

Individual doses f r mtherapy records andphantoni nie;~suremcnts

I'elvic sites,' leukaetnia, multiple
mydmia; lymphoma, all othcr sites

Benigngynnecologiml
disease117. 18, 1121

Mortality

4,153 exposed women
Age at expasure: 1388
(46.6)

United Stares

0-60

109,910(26.5)

Inm-uterine 2 2 6 ~ a

Individual doses frantherapy records andphantom mwsurcmcnts

Leukaemia,. 0th- haematolymphopcietic
wnccn, uterus,' Madder,. rectum.* othergenital,' colon, b e (in pelvis), liver:~ndgall-blrddcr, stomach kidney.
pancrws*

Pcplic ulccr

Mortality

1,831 expared pasons
1.778 unexposed persms
21.2% females
Menn age: 40

United States

20-48

77,757(21.5)

X-ray therapy

indiddual doses fromtherapy records andexperimental measurements

Stcmach,' d m ,pancreas,' lung*leukaemia; Frmdc breast,' oesophagus.
rectum liver, larynlg bone andconnective tissue, Madder, kidney, hrain,
thyroid, non-llodgkin's lyniphoma;
mydunlaIM81
Melropathia
hacniorrhagica

ID231

[GI1]

breast, ' skin

Diagnostic exnminntionc
Mnssncliusctts

Incidence

2,367 exposed ufonicn
2.427 uncxposd women
Age: 12-50 (26)

Unitcd States

0-250

54,WY
( 11.4)Multiple chest
fluaosqics

Individual exposures f r m
n i c d i d rcwrds and doses€ion] phantan
nicasurcmcnts andcomputer simulations

Brast*

Mortality

6,285 exp-cd persons
7,100 unexposed persons
49% femalcs
Age: 12-5U(26)United Stntcs

0->SO

331,206(24.7)

Multiple chest
fluoroscopies

Individual cqosurcs frommedial rccords and doses
from phantom
mcasuroncnts andn n p u t a simulations

Brcnsf' oe?iophagus,* lung, leukacmia

Mortality

18,940 cxposed w m e nlZ8OO uncxposcd womcn

Canada28-50

773,400(24.4)

Multiplc chcst
fluaoscopies

Individual cxposurcs I r a n
m e d i d records nnd rloscs
from phantm
mcasurcmmts

Breast*IT3 f l u a o s c ~ y(B311

Massachusetts

TI3 f l u a o s c ~ yID141

Canadinti '121
flttorosropy
IM191

%

UNSCEAR 1994 REPORTPopularim~studid
Sdy

Type of 3 r d ~Charur~crisrics

NuionJ origin

Follow-up

7brul
person(vears)years "

Typc 4aposure

Type of dosimetry

Cancers shalinl

homic Energyof Canada IJ~.
[G3, 1.1451

Cchat

8,977 subjects
0% fcmalcs

Canada1-r)

157,101

Nuclear and reada
research and related
technologies

R c e a d d exposures to
cxtcrml racliation

Leukaemia, all cancer

Ifanfad[G16, G I 1

Cvhvrt23,704 cxpsed nrcn
0% females

l l n i t d States (whites)

1-37

492,326(20.8)

Fxposurrs in nuclear
fud cycle and rcserch

Rccaded cxpasurcs toexternal radiation

Leukacmia, all cancer

Oak Ridge
National
Laboratory [G9,G17, W21]

Cohat

6,332 exposed men
0% females

U n i t d States (whites)

1-34

130,428(20.6)

Exposures in nuclear
fud cyclc and research

Rccaded exposures lo
external radiation

Leukaemia, all canccr

R a k y Flats

Cchat

5,8W exposed men
0% females

Unired Stales (whita)

1-28

82,721(14.0)

Exposures in nuclear
fud cycle and rcsrarch

Recuded exposures toexternal radiation

Leukaemia, all cancer

Cohort

5.0% cxpascd men
0% fcmalcs

Former USSR

35-40

167,790

Fspsurcr, in nuclear
fud cyclc and rcswrch

Rccudcd cxposura toexternal radiation

Iruhenria, all cancer[G17, WT]
Chclynbimk
18271

Envimnmentnl expcsurcs
Tccha River
[KIS]

China
hackgroundradiation, thyroid

Inridcnccl
mortality

28,WO exposed persons
394,000 uncxposcd
pcrsms '56% fcmolcs
0-90 ywrs

Former USSR (ethnic
Russians and'Ihrtar/l3aslrkirs

30

422,000(15.7) 1

Internal and extcrnal
cxposurcs to radionaive
waste discharged by
nuclear wcapns
production plant

Rough estimates of average
doses b a d on prclirninory
dose rcconrtruction efforts
and recent mcasurmcn(s dinternal doses

Lukacmia,' olhn canccrs

I'revalcncc

1,001 high b:~ckgound
1,005 low background100% females
A g : 5065

China

> 50

n.a.

ltighcr lcvcls d natural
background radialion

TLD, arcs and personal

Thyroid (nodules)853 cmtnnrina~edarws
813 u n c o o ~ r n i ~ t carmsdAge: rctal to >50

1:ornrer USSR

Releases andcnvironmcntnl
contamination frompower plant

Estimates of average doscby village

Thyroid (nodules)

Treatment d
hypcrthyradism

Avcrap administcrcd
activity (multiple~reatn~cnts)

Stomach.' kidney,' brain,' 4111 other sites

IW171
International
Cheroobyl
projca113, M211

Prcvnlcnce

n.a.

n.a.

mo~litors

Radiunt~clidesexposures: iodine
Swdishtherapeutic "'1[l112, 11271

Inridenu:

10,552 exposed persous
82% fcnralcs
Agc: 13-70

Sweden8-33

139,018(13.6)

Tt~hle2 ( c o n t i n u e d )~'opulI1l;Wi~ll&ad.OIudyVpe of 11dv
Charac~aisrics

"

'
f

x

Ndiand origin

I:ollo~up

Tor111
person(vcws)

years "

V p c oj dcuimcnyType oj aparu*c

C~meerss f d i dUnited States
thyrotoiaxis
s2]

Inddencc

21,740 cxpmed persons
12, I48 unexpoaul parom
19%f c m a l a
Agc: c10-80

United S t a t a0.30

271,000(8)

Treatment dhypathyradisrn

None

Lrukacmi% thyroid

Marshall Islands
fnllout[112R, R211

Prevalence

2,273 cxposed p a s m s
55% frniales
AKC: 5->60

Mnrshall Islands

29-2 1n.a.

Short-livcd
mdimuclidrr from
nuclcnr cxplosion

Estimated average dmc;
distance was nlso used aa
surrogate

Thyroid

Utah "'I fallcut( R 1 2 SJB,
S491

Case-mud

1,177 c n v s
5.3.30 c m t r d s

United States

up to 23nd.

Rllout horn nuclear
wcaponr t a t s

I3nred on rcsidcncc histories
and fallout deposition
rnudr

Lcukacmia"

Mean p n pcrwn in parcnthncs.
An natcrisk dcndea rites f u wldch stntisticslly significant cxccsws arc reponcd in the cxpuscd g o u p ( w h a t studits) rn for which n higher proportion of the a a c s wcrc cxpored to radiation ( a x - c m t r d studies).
Age nt cxpmurc, mean in parcnthcms.
Excldcx first five years.
Excluden first I3 years.
Thc distribution d pticnls is as follows: thyraid: 23 and 89; leukncniia: 25 and 90; bane sarcmas: 64 and 209 fop exposed and unexposed persons. respectively.
'The distribution d patien& is as follows: thyroid: 24 and 43; brain: 31 and 51: bone: 9 and 30; brcast: 8 0 md 190 f a exposed and u n c x p c d p e r m s , rcspcctivcly.
In thc ankylmingspmdylitis sample, 53% (7,431 perscus) u w c c e n s a d 18 months aficr a second course of lreatmcnt. P e r m s in this group havc an average d 3 . 5 years of fdlow-up. For Ihc remaining 47% (6,675 p m m s ) , the a v c r a p fdlow-up
is 23.6 ycan.
'Ihc control population in this study consists d the remaining population d uncxpoxd arws near the contaminated m e . h is n u a fix& cohuf.
Exposed group on1y.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

99

Table 3- Strengths and limitations of mrtjor epidemiological studies of carcinogenic eTCects of radiation
S~&YI

l+'eaknsscs

Sircngrhs

E x p o l u r n to s b m i c b o n ~ h i n pLife span s d y[P33, R23,
S7, TlS]

because d disease a occupatim;

Acuie, highdose-rate expasure that provides no d i r ~information on effects d gadual, low&-rate
exposures;

Wide range of doses;
Compreheasive individual dosimetry;S u n i v a s fdlowed prcspedively for m a c than 40 years;
Complete m a d i t y mzriainrnent;
Cancer incidence asmtainment

Restriaim to 5-year s d v u r s f w mortality (13-years w i v a s f a incidence);
Possible ~ t r i b u t i o nof neutrons 6anewh.t unmtain;
Possible cffeds of thermal M mechanical injury andccadtims fdlowing the bombing uncutain

Large population of all sger and both sexes no^ x l c c l dTreatment olmsliynant disease
Ccrvicai cancer cohort(sill

Largc5calc incidence study b a d on NmOUr registry
remrds;Long-term follow-up;
Relatively complete asccrtainmcnt d canws;
Nm-exposed comparison patients

Very large dose6 lo some organs result in dl-lolling andtissue damage;f a some
Potential misdusification of metastatic diorgans;
Potential misdahsification of exporure;
No individual doaimdry;
Characteristics d patients with Eervical c a n m differ ban
general population

Weal cancer
casezmtrd[B211

Comprehensive indibidual dosimetry for many organs;
Dare-response analyses;
Other soengrhs as above [88, I3 1 I]

As above [Bill except problem with inbvidual dosimetry
snd canparisms with geaaal populatim now rcmwed;

Contralateral beast

L a r p numbers d incident cases within populatim-hsed~ n o u regstries;r
Individual radiation dosimetry;
Wide range of high doses

Limited n u m b d young upomen;
Possibility d overmatching resulting in s a n e concordanced exposure between cases and rmtrds;
Potential misdassification of metastasa a recurrence

Comprehensive individual dosimetry f a bone marrow
mpartmcnts;ttoCmnprehensive ascertainment of t r ~ ~ n n e ninfamatim
separate chemotherapy risk;
Dcse-respoase analyses

Very large highdosc partial-body exposure to chest uall
prohbly resulting in cell-killiig

Comprehensive individual dosimetry to estimate organ
doses;
g
Attempt to adjust f a d ~ exposure;
Dose-respoase analyses

Only h i g h d m exposures;
Potential for m e overmatching since hapital-baud;
Complete dcsimctry not a l w y s available

QDCU

P18. S60]

Breast c a n a , adjuvant
radiolhcrapy[a]CMdbood cancers[TS,T6 nl

Small number of non-exposed casa;
Partial-body aad p a r t i d u g a n d d m e t r y complex

Trealmcnl of benign disease
Childhood skinhacmangioma
F 1 2 F15)

Long-term and complete follow-up;
Dosimdry for some cases and controls;
Incidence ascertain4
Prmaaed exposure to radium plaques

Relatively limitod range of doses tom& sites;
Relatively small number of specific caners

Ankylosing spmdyiitis[D61

Large number of expacd;
Long-term and complete mortality followup;
Detailed daimetry for leukaernia cases and sample dcohat;
Small non-exposcd goups evaluated for general assurance
that leukaemia risk was unrelated to underlying disease

Comparisons m'th general population;
Underlying disease related to c d m canca and possibly&a conditions;Individual dose estimates available only for lcukaernia cases
and a 1 in IS sample o f t h e population

Israeli tinea capitis
p 2 0 , RS, R 1 4

Large number exposed;
Two m t r d g w p s ;Ascertainment d cancer f r a n hapital records and tumour
registry;
Individual dosimetry f a many organs

h i m d r y for s a n e sites, c.g thyroid, uncertain due topossible patient movement or uncatainty in turnour I m t i o n ;Limited dose range

Relatively good dmc assasment F a skin and other cancers

Small number of can90recent fdlow-up information; few females

Individual rstimatcs d heast dose from medical records:
l n d d e n a ascertained;
Dose-response analyses

All exposed women were parous but c a n p i s o n women
were not (380 n o n - e x p d and sisters d both exposed andnon-cxpod);
Inflamed and lactating beas! might modify radiation &a

R15)

New Y o k tinea capitis[Al. 58. S61)
Ncw Y a k acutepost-pamm mastitis

LS~I

UNSCEAR 1994 IEI'OIW

100

Tahle 3 (continued)w

W c ~ t c

SomgrhrR d e s m thjmic
irradiation
Fizz SlO]

Lndibidual dosimetry f a thyrcid and some dher sites;
Sibling m t r d group;h g fdlow-up;~
be evaluatd;
Ractimation d f c muld
Dcbe-response analyses

Radiation treatment fields on newborns varied anddosimetry f a some sitca uncertain;
Adjustment in analysis f a sibship sizz unmtain:
Questionnaire fdlow-up may have resulted in unascmaincd
cases

Benip gpxcalo&al
discase[DU.17.14 1121

Large number of ex@;
Nm-exposed wmwn uith benign gynacmlogical disease;
Very l m g mortality fdlmv-up;
Indi\idual dosimetry;
Provaded exposure to radium implants (10-24 hours);
Dose-response analyses

Uncertainty in proportim d aaive bme-manowcxpored;
Small numbers d certain -1;
Midassificatim d m a i n c a n a r s on death certificate+such as panucis

Peptic ulcer
IG111

lndividual dosimetry;Nw-expmed patienu with peptic ulctr;
F~ccptimallyl m g fdlmv-up (50 years);Some risk factor infamation arailable in recads

Standnrdi7d ndiothcrapy precluded dwe-response analyses;
Non-homogeneous dcnc distribution uithin organs such that
simple avexaging might be misleading
Metastatic spread d stomach canca nas probably
mixlassifiad as l i v a and pancreatic m c r r on deathcertificates;
Possible selection of s a n c u b t unfit patients forradiothnapy rather than surgery

Diagnostic cxnminsti~n~r
Masachusctts TB
flu0r-yp 3 1 . B41,Dl41

Incidcncc study with Img-term fdlow-up (50 years);
Individual dosimeiry b e d on pticnt r c m d s andmcasurcmmts;
Nm-exposed TB patients:
Franiaralcd uposures n c u n e d over many years:
Drse-responsc analyses

Uncertainty in dose estimates related to fluoroscopic
exposure time and patient oricntatim;
Questimnaire r a p m s c probably u n d c r a d l x d cancers;
Debilitating effect of IB may have modified radiatim cffed
for sane sites, in particular che lungCanadian TB
fluormpy~
1~

l a r p numberr
Noo-exposed TE comparison groups;
Individual dosimelry f a beast;
I'racticmated exposure o v a many years:
Dare-raponsc analyses

Mortality limits m p a r i s m r uith incidence series, e.g. time
response;
Unccrtaintia in dosimetry limit prcdse quantification drisk
DitTcrcnt d m e response lor one sanatorium and rest of
Canada may indicate errors in dosimetry, differential
ascertainment of cancers, or bidogical r a p c a r e

Adol-cc
poeiMy a vulnaablc age for exposure;
Dosirnary ancmpted based m number of films and breast
cxpaure;Dose response attempted

Comparison uith gcncral populatim polentially m i d d i n gsince disease associated uith vvcral breasl c a n m risk
factors, such as nulliparity;
Small numbers (11 cancers) compared with 6 expcetcd;
Onc mca d a e d c d incidentally during special snccning1

Scdiosis[ru41

Prenatal exposures
O d o r d s w e y ofchildhood cancers
p23. M22 S37.
S52]

Very large numbers;
Comprehensive d u a t i m d polentlal d a r n d i n g
Early nmcems o v a r a p o m c bias and sdenim h a s
resdved

Uncertainty in fetal dare from obstetric x-ray exarninalims
precludes p r m s c estimate d radiation risk:
Similar relative r i s k for l e h e m i a and a h a d i d e a a o ~ ~ s
may point to possible residual d w n d i n g

New Englandchildhmd cancer
1~91

Larke numbers;
Reliance m obstetric recads to determine exposure

Uncertainty in fetal dare prcdudn prcase estimate c€radiation risk

Twin studies

llighcr propmion of twins than singletons received obstetric
x-ray examinations for rcasons unlikely to be due tomaternal illness

Small numb- of cancers in general;
Uncertainty in fetal dose precludes radiaticn risk estimate;
For cohort studies, actual propatim expoaed andcanparisms with sindc births add unmtainty

Not selected f a e x p u r c ;Reasonably accwate est~mateof dart;
Mortality fdlow-up relatively cmplctc:
Follow-up until early adulthood

Small number of exposcd indinduals and small nurnbcr d[H3,llS. MU.
M3Z R13. Rlb]

S u n i v a s of atomic
bombings[Yl. yz y3]

cases;

Incidence determination may w t be m p l a e ;Mechanical and thermal effects may have influenced results

Hadionuclidc txpoaurcs: i ~ d i n r
Diapartic I'll

PIU. IUT]

Large numbers:
Nearly canplete zrcatainment d a n c m through linkage
with cancer regisuy;
Administered acti\itics of "'1 knoun for ear3 patient;
Lowdcse-rate exposure

Comparison uith general pqulatioo;
Reason for some examinations d a t e d to high d c t m i m dthyrad cancer& i.e. suspicim d thyroid hrmw uas dtm
carect;1)oses to organs other than thyroid very lm;
l'opulation under =I\-cillanceANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

101

Table 3 (continued).Q=6

Sfryrurgfhs

IVeakneuu

United States
thyrdoxicais
P 9 , S2]

Large numbers d patima treated with 13'l;Large non-exposrd comparison groups;
Comprehensive followup effort

Individual radiation dose n u computed;
S h u t follow-up, not rcccnt
Only leukacmia and thyroid tumoura d u a t e dSatedish 1 3 1 ~hyperthyroid

I a g e numbers;
Nearly canplete incidence ascertainment;
Administered activities of "'I known;
Low-dose-rate exposure

Comparison with general populatim;
Dare response n d b a d on o r p d a a ;Highdose cell-killing probably reduced passible thyrdd
ettea;
Patients selection for treatment

Population unselected for exposure;Comprehcnsivc medical lmg+mn fdlowup;
Indibidual dosimetry attcmpied

Mixture of n d i a d i n c s and gamma fields preclude accurate
estimate d dosq
Surgery Pad hormonal therapy probrMy inIluena
subsequent acurrence d thyroid neoplasms;
Small numbcrs

Clinical c s m i n a t i m s f a thyroid canComptchcnsive d k m e u y assessment ananpted;
Large number of lark.crnia deaths;
Pruraded exposures at low rate&eat uncertainty in accurately estimating dosc to thyroid
and bone manow:
Estimated cumulative dowr much Iowa thm cxpnienced
from oat& hackground radirtim;
Possible recall and sunrillance tiasp@]Marshall Islands fallout

IH28, R211

Utah *'I fallout
p12, S48. S49]

Environmental t x p o s u m

T d a Riva
P<l8]o l i n a backgrcund
radiatiw, thyroid[W17]

Intcrnatimal Qlcmobyl
project[I3, M21]

Large n u m b s expmcd uith relatively l m g follow-up;
A uide range d estimated doses;
Unselectd populatiaq attempted usc cf local populationr a t e for comparison;
Possibility to evaluate c h i c differences in cancer risk
Shows great potential f a future studies

Dosimetry difficult and n u indhidual;
Quality of minure d i n l a a d and e n a d exposures
canplicata dosimetry
Follow-up m d canccr armtainment uncertain;
Contributim d chemical expcsurcs uncvaluatedl3lind clinical examinations of exposed and non-exposed;
lifetime exposure to low doses at low dose rate;
Blood s t u Q e to confirm exposure;
Extensive dosimetry f a region;
Stable population;
Low prevalcncc of x-ray exposure;lligh participation rate;
Aascssment of possible confounders

Approximately onc third d life-rpan expaed as children;
Factors other than radiatim levcls existed that could not be
evaluated;
High prevalence of s mild goiter might have hindered
detection of thyroid nodules:
Dares very low

h i m d r y ascssment f a highly contaminated and contrd
villages;
Physical examination f a thyroid nodules diseare using
ultrasound

Limited fdlow-up ancr accident (4.5 years) predudedd e t e d m of possible rirk;
Precise dosimetry uncatain
Small sample size

Occupalional exposures

Nuclear n w k m[BZ.D1Q Gl6,
G17. K20]

Oncn large numbers;
Pcrromd dosimetry;Low-dare fradimatcd exposures;
6 u l d problde useful information in future

Doses w l w that clcar danonrtratim d radiation dfm
difticult;
Possibly confounding influence d chemical. a a h o s anda h 4 toxic e x p u r e 5 in workplace;
Healthy w a k n effed:
Sfataiity fdlou.-up:
Lifestyle h a a s , such as m d d n g histaria. n u availaMe

Medical workers

O f t a large numbers;
h d o s c fraaimated cxposure o v n very l m g periods

Lack d infamation on i n d i d u a l dmes precludes
usefulness to date

[A9, B39, E7. M24.
S38, W141UNSCEAR 1994 REPORT102

Table 4Comparison of incidence and mortnlity data for solid tunlours in Lirc Span Study of survivors of lhe atomic
bombings(TI 51
Cancer rypc

Oral cavity lad pharynx

N u m b u of incidau cares 1958-1987

N&of dmth 19501987 "

132

79

185

211
2365

Diprive r p t m"-0Ph.w
Stmch
a m

a658
457
35 1
585
295
240

Rectum

m

Orhn

26

Z73
76 1
187
243
91

Taal

4797

4408

55
80
872

20

51
52
816
22

Taal

1027

941

SLin
Mdamma(hhw skin

13
168

28

Taal

181

36

F C ~ ~ hem
IC

n 9

186

Utninc corpus
Chary
Othn

66
553
85
133
34

315
110
15
104
31

~

89 1

ns

Male genital
Prostate

140

Otba

20

69
6

Taal

160

75

104

Oh-r

210
73
28
14

Tdal

325

1%

Nmous systcm

125
225
22 1

75

307

8,613

6,887

Liver
Gall-bladda
PvlacprRespinlory system
Nasal cabjlyhT m c h q b d w ,lung
Otha

Fcmale genital
Utavs. not &mi%rpccificd

W

x ocri~al8Urioary system
Bladder
KidoeyRenal pelvis and urctn

lhyroid(kha d ill-dcfincd rita

Tdal

45
4

3

49

-

In s a n e case6 the n~imbaof d e a b c x d the n u m b otinadcnt casu. l h n e are variws reasons f a this. firs^ the rnonality fdlow-upis more thanyears l m g a than thc f d l o w u p f a the inadcncc dl(.. Secondly. f a m e sites, e.g. the liver and the pancreas, death oatifrcale d i r p a i r is p m . For aha,c.g. the uterus, no detail i s prondcd.

ANN= A: EPIDEMIOLOGICAL Sl7JDIES OF RADIATION CARCINOGENESIS

103

Table 5
Summary risk estimates for solid tumours derived from data on survivors of the atomic bombing a

Cancer mortality [S7/1950-1985*

Canccr morrality [R23] '1950-1987

Cancer incidence [TIS]
1958-1987

Cancer type
Excessabsolure risk
(16 pys,g-'

Excessrelatiu risk
(sv-')

Salivary dand
Onl cavity
Digestive system
O-Phagus
StomachNu reported
Not reported *0.3 (0.24.4) 'NU reported
Nu reported

Excessrelative risk
(sv-')

Excessnhcolufc risk
(104 PYSII-'

Ercessrelaliw riot

Nu reported

Excessohsolute risk
(10' PYSV)-'(sv-')&Y
Prartate
Urinary tract
Urinary bladda
Brain and CNS'Ihyroid

0.6 (0.1-1.2)
0.3 (0.1-0.4)
0.9 (0.4-1.3
4.09 (4.2-0.4)
0.1 (c-0.2-0.7) f
0 5 (411.6)
4.2 (c-0.2-0.4)
1.9 (0.3-0.9) '0.6 (0.3-1.0)
0.2 (~4.2-2.5)
1.2 (0.6-21) '0.4 (0.024.8)
1.3 (0.5-23) '0.1 (c-0.2-0.9) '1.3 (0.5-24)
1.4 (0.5-29) 'Not reported g
Nu reported

4.0 (27-5.4) '0.5 (0.1-0.9)
2 4 (0.5-3.5)
0.8 (0.4-1.3)
4.1 (c-0.2-0.6)
0.2 (c-0.2-0.5) f
0.3 (4.03-0.7)
4.1 ( c . 2 0 3 )
1.8 (1.0-27) '1.7 (1.0-25)
0.0 (~-0.2-0.12)
1.2 (0.6-1.9)
1.0 (0.07-21)
0.7 (0.2-1.3)
0.0 (~-0.2-0.9
0.7 (0.3-1.1)
0.5 (0.2-0.9) 'XU reported 5
XU reported

Not reporled-0.2 (c0-0.3)
0.3 (0.2-0.5)
0.6 (0.09-1.3)
0.2 (0.1-0.4)
0.5 (0.1-1.2)
0.1 (c-0.2-0.6)
0.5 (0.2.0.8)
0.3 (-0.1-LO)
4.2 (c-0.24.2)
0.6 (0.3-0.9)
0.7 (0.3-1.0)
0.31 (~-0.1-1.5)
1.3 (0.6-2 1)
0.1 (~-0.2-0.6)
L2 (0.2-28)
0.3 (-0.2-1.6)
L3 (0.4-26)
1.5 (0.3-5.3)
0.4 (-0.1-2.0)
0.094 (c-0.1-1.4)-0.1 ( ~ 0 4 . 1 )
5.1 (3.0-7.3)
0.5 (0.07-0.9)
1.9 (0.5-3.5)
0.5 (0.06-1.1)
0.1 (c-0.3-0.6)
1.3 (0.5-22)
a 2 (-0.07-0.6)-0.2 ( ~ - 0 . 3 4 2 )
2 0 (1.1-3.0)
1.9 (1.0-29)
0.03 ( ~ 0 0 . 1 )
1.3 (0.6-21)
0.3 (~-0.5-1.4)
0.7 (0.1-1.4)
0.2 (-0.1-0.9)
0.7 (0.2-1.2)
0.5 (0.1-0.9)
0.1 (0.04-05)
0.016 (<-0.03-0.2)

1.8 (0.26.0)
0.3 ( 4 4 . 9 )
0.4 (0.3-0.5)
0.3 (4-1.0)
0.3 (0.24.5)
0.7 (0.3-1.3)
0.2 (-0.2-0.8)
0.5 (0.24.9)
0.1 (4.24.7)
0.2 (c-0.24.8)
0.8 (0.5-1.2)
1.0 (0.6-1.4)
1.0 (0.4-1.9)
1.6 (1.1-22)-0.2 ( 4 3 4 . 1 )
1.0 (0.2-23)
0.3 (4.1-1.2)
1.2 (0.6-21)
1.0 (0.3-2 1)
0.3 (-011.3)
1.2 (0.5-21)

0.2 (44.7)
10.4 (7.0-14.0)
0.3 (d-1.0)
4.8 (25-7.4)
1.8 (0.7-3.0)
0.4 (-0.4-1.5)
1.6 (0.5-29)
0.2 (~-0.4-1.1)
0.2 (~-0.4-1.1)
4.4 (294.1)
4.4 (296.0)
0.8 (0.4-1.4)
6.7 (4.9-8.7)-1.1 (-1.9-0.7)
1.1 (0.2-23)
0.6 (4.3-22)
2 1 (1.1-3.2)
1.2 (0.3-2 1)
0.2 (-0.1-0.8)
1.6 (0.8-25)

All solid turncurs

0.40 (0.3-0.5)

10.1 (7.8-12.4)

0.45 (0.3-0.6)

11.1 (8.4-14.0)

0.63 (0.52-0.74)

29.7 (25-34)

Cd~n
Rmum
Livu
Gail-tdadda
Pancreas
Rcrpiralary syncm
N m - m d a n ~ mshn
Female brew
U t e ~'NU reported

90% a given in parentheses.
Based on organ-absabd dosc (ncu~rcmRUE a 1).
Basd on weighted dose in the organ (neutron RBE = 10).
Shielded-kcrma-based excess rclativc risk and e x c a r absolute r ~ s kestimates for canurrs d ~ h cnose (0.2 and 0.03, respectively), larynx (0.5 and 0.1). andpharynx (-0.4 and -0.02), and tongue (-0.6 and -0.02) are presented in [Sq.
Values d n i w d 6om shielded-kcrrna risk cstimates in [Sq.
Based a cam explidtly coded as primary on the death ccrtificatcs: c x d u d a cases n u cxplidtly coded as primary or secondary. inclusion of such caws leads
to an ERR estimate of 0.46 (0.2-0.8).
Shidded kcrma-bored excess relalivc risk and cxabsolule risk estimates far malignant brain tumours (0.03 and 0.01. rspcctivcly) and dhcr CNS turnours( 2 1 and 0.1) are presented in (S7J.
Lodudes livu cancer deaths specified as primary and also those specified as either primary or secondary.

Table 6
Summary risk cstimatcs for lympho-haematopoietic tumours derived from data on survivors of the atomic
bom bings

Conccr mortal* 1950-19SS [Si] "Cancer rype

Lcukaemia
LymphMultiple myelomaaExcess relarive risk

Cancer incidence 1950-1987 (P33/

Excess absolute risk
(I O'PYSV)

E x c m rdarivc risk

(sv-I)(sv-')

Eucrc absolu~criskpysv)-'

5.2 (3.8-7.1)
4.1 (c0-05) C
2 3 (1.7-6.3)

2 9 (24-3.5)
0.0 (c0-02)
0.3 (0.1.0.5)

4.4 (3.2-5.5)-0.1 (c0-0.7)
0.4 (4-1.7)

2 7 (22-3.2)
4.1 (cO-0.5)
0.1 (cO4.4)-'

Based on organ-abrabtd dosc (neutron KBE = 1).

Based cm wcighted d w in thc o r p n (neutron RBE = 10). Estimates derived from summary tables in [P33].
Values d a i w d From shielded-kcrma risk estimates in [S7). Indudes both Hodglrin's and non-Hafgkm's mscs.
Nan-Hodgkin's cascs only.

PO'

UNSCEAR 1994 REPORT

104

Table 7
Cancer incidence and mortality in survivors of the atomic bonibings

Ahsorbed dare

Mean weighrui dare

Person-years

N u m b of subjsrs

Obvvd

Erpccred(Sv)

Solid Urnour incidence, 1956-1987IT151

d.01
0.01-0.1
0.1-0.2
0.2-0.5
0.5-1
1-2
>2

0.00
0.01
0.14
0.33
0.74
1.42
252

893,767
454,734
113,414'124,131
60,09630,031
6,175

42,70221.479
5,307
5,858
2882
1,444
300

4,286
2223
599
759
418
273
55

T d

0.11

1.682349 '

79,972

8,613

8,103

4,281

2 174
553
637
290
146
2ll

Solid tumour mor(8lity, 1950-1987(R231~0.01
0.01-0.1
0.1-0.2
0.2-0.5
0.5-1
1-2
>2

Tdd

0.14
0.33
0.74
1.42
252

1,385,374
693.935
171130188.44493.116
46,891
9,984

46,17623,147
5,713
6,283
3,111
1.543
336

3,435
1,868
472
582
312
178
40

3,433
4837
444
508
234
108
18

0.11

2588,873

86,309

6,887

6.581

81
42
11

0.00

0.a4

Leukaemis incidenct, 1950-1987[P33]

'

~0.01
0.01-0.1
0.1-0.2
0.245
0.5-1
1-13
1.5-2
2-4

0.00
0.04
0.15
0.34
0.76
1.35
1.92
2.83

1,166,110
609,964'
155,982
167,675
85,711 '31.29515,082'
11,101 '45,15923,304
5,880
6,387
3,304
1,209
584
444

90

Total

0.12

2242919

86,271

231

38
8
27
24
19
8
17

12
6
2
1
1
156

h e categories arc detined in terms of unwcighted intestinal doses fa solid turnours and unwcightd bane marrow doses f a leukaemia.
The mtan doses arc expressed as weighted iotestinal dcses for sdid tumows and wcightd hone marrow doses f a leukacmia (RBE fm neutrons = 10).
Person-years adjusted fa migration.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF R4DIATION CARCINOGENESIS

105

Table 8Risk estimates for cancw incidence and mortality from studies of external low-LET exposures
I7re nun& of o b s d Md apec~edcorer or well as (he m a n dan and pcrsm-yews fa c h r r sndies are c ~ l p u r t dthroughour this Table for apatarl
persons only. In rhe life s p s*~ the cgpased group included surviwrs wdh o r g darts~of 0.1 Gy a more

PART I: OESOPHAGUS

oh-

MY

M-

dart
(SvJ

persony ems

n

65.5
13.7
4.5
74.7

0.24
0.23
0.24
0.23

84

78.9

12

11.0

Cases

cases

Amage
rdruive rkk

AVQa8ecsv-',

absolwe risk '(la'PYsv)-I

298,700
493.900
365,200
427.300

0.16
1.06
3.32
0.13

0.35
0.29
0.41
0.24

0.23

788,5800.29 (-0.2-1.0)

0.29 (-0.2-1.0)

0.35

178,243

0.26 (~-0.2-22)

0.16 (~-0.6-1.4)

0.58
0.36
0.13
0.75

Incidence
Life span study [TlqSex
Age at exposure

Male
Femalec20 yean>20 YWSA1l

O n i c a l cancer cohort [Bl 11

*

68
17
8

Mortality
Life span study [RZ]
Sex

81
22
8
95

74.7
16.1
6.2
84.6

0.23
0.23
0.23
0.22

471,800
nL300
574,500
628,600

0.37
1.61
1.20
0.56

103

90.8

0.23

1,203,100

0.59(-0.0-1.4)

0.44(<0-0.9)

Massachusetts lB flumarcopy ID141

14

13.8

L06

l69,4Z

0.01 (-0.2-0.6)

0.01 (-0.3-0.4)

Ankylosing spcmdylitis [D6, Ld]

28

12.7

4.00

183,749

0.30 (0.1-0.5)

0.21 (0.1-0.3)

Age at exposure

Male
Femalec20 years
2-20 years

AU*

90% CI in parentheses derived from published data for the life span study and using exaa Pcisson rnc~hodsFor the other studies.
Excludes cases during first 10 ycan d Followup.
PART 11: STOMACH

Ohrovedcaw.

MY

Expected

Mean dose

Person-

caser

ISvJ

Yws

(sv-I)

Avsage aces
ohsolure risk '(la' pusr.)-'Average a c e s
rdative risk a

Incidence
Iife span study [TI51
Sex

679
628
167
1140

660.4
561.3
1420
1079.7

0.24
0.23
0.24
0.23

298.700
493.900
365,200
427.300

0.12
0.52
0.74
0.24

261
5.86
287
6.15

1307

1221.70.23

792,500

0.30 (0.2-0.5)

4.68 (25-7.4)

348

117.3

200

aa.

0.54 (0.1-1.5)

0.37 (0.03-1.0)

0.24
0.23
0.24
0.22

47 1,800
73l,300
574,500

1067

623.0
484.5
91.2
1016.3628.600

0.17
0.26
0.22
0.22

230
1.75
0.35
3.51

1163

1107.50.23

1,203,100

0.22 (0.10.4)

2 0 2 (05-3.5)

Ankylosing spcmdylitis [Db,Lb]

55

54.3

1.65

130,6160.01 (-0.1-0.2)

0.03 (-0.5-0.7)

Benign gynaccological disease (181

23

21.8

0.B

n.878

0.28 (~-0.2-25)

0.78 (-2.6-4.6)

Peptic ulcer [Gll]

40

17.4

14.80

35.8150.09(0.05-0.14)

0.43(0.2-0.7)

Metropatha hacmorrhadca [D23]

33

26.8

0.23

47,1441.01 (~4.2-28)

5 . n (c-2.4-16)

Age at erposure

Male
Female4 0 ycan>20 ycanAll

Weal cancer casecoanol [B21]

MorCslity
Life span study [R23]Sex

Age at exposure

Ma1eFemale4 0 years>20 years

All

649
514
%

" 90% CI in parentheses dcrival from published data for the life span study and using cxaa Pcisson methods for the other studies.
The c x m s atadutc risk estimate was computed using badtgrwod incidence rates estimated using the &cat
cancer what study [Bll].
The otaerved and expected number d cases are for 10-year smivors. ' h e estimated number d expcaed cases incorporated aa adjustmetit based upon the
Poison regression model given in Pa].

UNSCEAR 1994 REPORT

106~hsmvdcma

Yudy

Erpcrrdc a a~ e a dosen(SV)

Personyears

Araa'erelative risk
(sv-I) a

ohsolvte risk
(idPYSV)"

incidence

Life span study [TI51
Sex

Male
Femalec20 years>20 y m s

Age at exposure

All

p21]

Cenical cancer case-control

109
114
32
191

90.7
103.0
28.0
165.7

0.23
0.22
0.23
0.22

297,500
491,100
363,300
425,300

0.87
0.48
0.62
0.70

266
1.01
0.48
271

223

193.7

0.23

788,600

0.67 (0.1-1.3)

1.65 (0.7-3.0)

409

409

24.0

n.a.

0.00 ( O . ~ . O l )0.00 (O.OO-O.01)

Mortality
Life span study [RZ]
Sex

63
66
11
118

56.8
9.7
9.6
106.9

0.23
0.23
0.23
0.22

471,800
731,300
574,500
628,600

0.47
0.47
0.60
0.47

0.9
0.38
0.10
0.80

129

116.5

0.23

t203,lOO

0.47 (0.1-1.1)

0.45 (0.3-1.3)

Benign paecological disease [I81 '

75

46.6

1.30

77,8780.47 (0.2-0.7)

281 (1.54.4)

Peptic ulcer [Gll]

25

20.6

6.00

118,300

0.04 (0.0-0.1)

0.07 (0.04.02)

Metropathia haemonhagica ID231

47

33.0

3.20

47.1440.13 (0.03-0.3)

0.93 (0.2-1.8)

MaleFemalec20 years>20 years

Agt at exposwe

AU

'
'

9046 Q in paretuhcxs derived CTUU published data €or the life span study and using exact Poisson methods for the other studies.
The excess atsdute risk estimate was computed using background intideoce rates estimated using the cervical cancer cohut study [B12].
The o b a v e d and expcaed number d cascs are for 10-ycar surviwrs. The estimated number oC expected cases incorporated an adjustment based uupoa the
Poisson regression m d d given in pa].
Inmrpaates a standardized mortality ratio based upon internal amparison model in [18].
Since the original paper prorides only a range d doxs for this sire, the value given here is a very crude estimate.
PART IV: UVEH

-Q~Y

OhrtrdErpcrred

casa

cwcs

(st4

Personyears

Average a c a s
relatire rink(sv-')

Awagc a c e s
crbsolute risk "(10'Pysv)-'

Mean dose

Incidence
Life span study [TlS]
Sex

Male
Femalec20 years>20 years

Age at exposure

All cases
Total (miuoscopically verified)Ccrsical canccr cohort

pll]

174
110
63
221

151.5
107.2
47.2
211.4

0.24
0.23
0.24
0.23

299,600
496,600
367,000
429.200

0.61
0.11
1.39
0.19

3.09
0.24
1.78
0.95

284
109

256.6
94.7

0.24
0.24

796,300
796,300

0.41 (0.2-0.9)
0.64

1.33 (0.5-2.9)
0.76

19

20

0.70

342786-0.13 (c0-0.9)-0.03 (44.2)

Mortality
Life span study [RBI
Sex

Male
Femalee20 years>20 years

202
150
56
29 6

178.6
141
43.4
276.2

0.24
0.23
0.24
0.22

47k800731,-30
574,500
628,600

0.54
0.27
1.26
0.31

204
0.53
0.90
1.35

All cases
Tdal (primary on death certificate)

352
48

319.6
46.2

0.23
0.24

1,203,100
L203.1000.44 (0.24.8)
0.16

1.18 (0.5-22)
0.06

h a k y l a i n g spcndylitis [D6,L61

6

5.6

1.60

130,6160.05 (<0-0.7)

0.02 (c0-0.3)

Bmign paecrrlogical di-

9

16.6

0.21

77,878-0.5 (-0.5- -0.3)

c-1 (c-1- -0.5)

Peptic ulcer [Gll]

9

9.0

4.60

35,8150.00 (c0-0.2)

0.00 (4-0.4)

Mctropathis haen~arhagicap 2 3 ]

2

6.0

0.27

47,144-0.5 (c-0.5-0.2)

c-0.2 (cd.6-0.2)

Age at exposure

"

[IS]

90% a in parentheses derived horn published data for the life span study and using exact Poisson methods for the other studies.
Exdudes cascs during Erst 10 years d follow-up.
Estimate is b e d on deaths coded as primary liver cancer u liver cancer not specified as secondary or primary.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESlS

107

PART V: LUNG

ohQ1-&S~&Y

FLlFCF

CUCF

M~~~
IS4

personyews

A'wagercla~iverkk(sv-') "Awage
absolute r i d '(10' PYSV).'

Incidetlte
L f e span s ~ d [yT U J
Sex

Male
Female4 0 years>20 years
5-19ycarr
20-29 years
30-42years

426
85
146
25

224.7
140.1
26.2
338.5
67.8
116.3
186.4

0.25
0.24
0.25
0.24
0.24
0.24
0.24

302000500.700
370.000
432700288,566
317.535
314,545

0.36
208
0.57
1.06
1.01
1.05
0.85

267
5.81
0.41
8.27
245
3.85
5.05

456

564.7

0.25

8027001.00 (0.6-1.4)

4.55 (246.0)

11
135
227

214.7
149.0
29.8
334.0
635
903
194.4

0.25
0.24
0.25
0.24
0.24
0.24
0.24

47l.800
m300
574.500
6 W m
566,780
316,912319,418

0.21
1.59
-0.38
0.88
0.48
201
0.69

0.95
3.24
4.20
4.68
0.54
5.80
4.19

433

363.8

0.25

1,203,100

0.76 (0.3-1.0)

230 (1.0-2.9)

224

184.5

1.80

130.6160.12 (0.04.2)

1.68 (0.7-2.8)

Massaefiusem 1B fluoroscopy ID141

69

81.8

0.84

169,425

4.19(<4.2-0.04)-0.90 (<-1.84.2)

Pcptic ulca [Gl11

99

58.4

1.80

35.8150.39 (0.24.6)

6.29 (3.8-9.1)

Age at e x p o w elime dncc expuure

All

245
211

M

Morbliryl i f e span study [R23]Sex
A p at uporure

lime s n c c expaure

Male
Fade
4 0 yam>20 y a m
5-19years
20-29y a r s
30-42 years

All
Ankylaing rpcmdylitis p,L6]

226
207
27
406

-

"

90% (3 in parentheses derived I r a n published data for the life span study and using exaa Poisson rncthob for the other studies.

PART VI: BONE A\'D CONhTCTNE TISSUE

Okcrwd

sudy

CPICF

Erpcrlod
C ~ C F(S'l

Pcrsonyeas

A ~ w a g ca c e s
rclalivc riat
(sv-9 aAwagc a r e sabsolute riat '(I 0'PYS")-~

Mean darc

Incidencel i f e span study [TI51
Sex
Age at c q o r u r e

Mde
Fcrndc<20 y a m
>20 years

All
Skin haanandoma [FlZ]

9
7
4
12

6.4
5.7
1.1
11.0

0.23
0.22
0.23
0.22

297.500
49l.100
363.300
425,300

1.78
0.99
11.0
0.42

0.38
0.12
0.34
0.11

16

121

0.23

768,W

1.42 (<-0.245)

0.22 (<4.1-0.7)

8

29

0.4

379,263

4.33 (0.94.8)

0.33 (0.14.8)--

Qlildhood m d i o k a p y [T6]

54

20.0

27.0

n.a.

0.06 (0.01-0.2)n..

Mortalily
Life span study [R23]Sex
Age at exposure

Male
Fcmale<20 years>20 years

All
Ankylosing spmdylilis [D6,U]@one mly)

14
10
3
21

10.8
8.5
1.9
17.4

0.23
0.23
0.23
0.22

471.600
731,300
574,500
628,600

1.26
0.81
258
0.92

0.29
0.09
0.M
0.26

24

19.3

0.23

1,203,100

1.07 (<-0.2-3.3)

0.17(<-0.1-0.5)

4

1.4

3.00

130.6160.65 (0.00-1.9)

0.07 (0.00-0.2)

90% (11 in parcnthcscs derived f r m published data for the life span study and using exna Poisson methods for the &a studics.

UNSCEAR 1993 WI'ORT

108PART VII: SKIN (NON-AfIIIAVOMA)MYA ~ w a g ca c u s
relari~rrisk

Aveoge a c r s

(SV+

(10'
PYSV)-'

324,100
538,900
399,300
463,700

0.92
0.88
5.37
0.39

0.89

Ohsend&pufcdMean dace

cares

casu

(.W

Persony carsh [ w c risk 'lncidrncc

Life span study [TlS]
Sex

Male

41

31.4

F C ~ ~ Cn

44.4

c20 y u r r
220 ycan

21

n

7.7
68.2

0.33
0.32
0.32
0.33

NI

98

75.9

0.33

863,000

0.88 (0.4-1.9)

0.78 (0.4-1.4)

Israeli tinem capitis [RlO. R19]

42

10.0

6.8

265,070

0.47 (0.34.7)

0.18 (0.14.25)- Cenical can= cavcootrd [B21]

60

85.7

9.6

32786

0.01 (4.024.01)

4.02 (-0.M4.03)

83

24.0

4.5

52,OOO '0.55 (-0.024.01)

250 (1.9-32)

14

4.2

23

87,000 '1.04 (0.5-1.9)

0.50 (0.24.9)

80

75.3

9.6

122WO '

0.01 (-0.014.03)

0.04 (-0.08-0.2)

Age at exposme

X m Y a k t i n u apitis (uhites) [ ~ 6 2 ]Rochester thymic irradiation[S62]

Massachurc~uTB fluorasmpy

a

[S62]

o. n
1-04
0.58

NR Y a k maailis

[S62]

14

10.7

2.6

14.WOC0.12(-0.08-0.4)

O.W(a.6-3.1)'Ihymid inadiahm[S62, 563)

63

45.0

3.8

9.000

0.1 1 (0.034.2)

0.M (0.24.9)

90% CI in parcn~hcseddmved horn published data for the life span study and using exnct Poisson mefhods for the olhcr studies.
F r a n data ptescnted in a review paper by Short [S62].
Pcrson-yearsestimated born data in the review p a p a by S h a e [S62].

ANNEX A: EPlDEMlOLOGlCAL STUDIES OF RADIATION CARClNOGENESlS

109

PART VIE EMNH B R L G T

Ohm&
cniu

S~U~Y

ErpccredC ~ L I

ac6s

Mean &sc(St,)

Persony ea-s

A'waKcrelative ruk(sv-') "aholure risk '(10'PYSV)-'

Incidence
Life span study IT151
Age at exposure

122
173
49
87
159

62.8
137.1
36.9
63.5
995

0.28
0.27
0.28
0.n
0.27

202600308.000
161.400
175,800
173,400

3.32 (2.34.4)
0.98 (0.4-1.6)
1.19
1.34
221

10.3 (7.2-14)
4.36 (1.8-7.2)
272
4.86
12.68

295

199.9

0.27

510,500

1.74 (1.1-2.2)

6.80 (4.96.7)

Mawchusctts TB f l u o r a q y 10311

142

107.6

0.79

54.6000.40 (0.24.7)

7.98 (3.6-13)

New Y a k acute post-prmrm mastitir [S91

54

20.8

3.70

9.800

0.43 (0.34.6)

9.14 (6.0-13)

Aakylming spcadylitis [D6.U ]

26

16.1

0.M

22033

1.24 (0.3-25)

9.01 (20-18)

Suzdish beas!irradiation [RI. Ma]

115

288

8.46

37.4000.35 (0.34.4)

272 (2.2-33)

Cenical canm cacamuol ' [B21]
W~thorno r a r i a953
911063.0
82.6

0.31
0.31

a a.
n.a.

4.2 ( ~ - 0 . 2 4 3 )0.33 (c4.2-5.8)

c-0.3 (c-0.3-0.2)&a.

Cootrducrd heas!
b a r k [SbO]
United States [B18]

529
655

508.7
550.4

251
282

&a.
0.8.

0.02 (c4.14.2)
0.07 (<4.1-0.2)

n.a.
n.a.

22

7.8

0.76

38,200239 (1.24.0)

4.89 (2.4-8.1)

Skin haanangioma IF121

%

36.4

0.20

379.283

4.2 (1.8-7.2)

4.1 (1.86.9)[IIZJ]

11

6.1

0.13

21.691

6.37 (0.9-15)

17.8 (2.443)

25

6.1

4 . 0

lO0.057

0.07 (0.04-0.11)

0.04 (0.03-0.07)

Xrnc since cxposurc<20 years>20 years
5-19 years
20-29 years
30-42 ycars

All

Rochesta thymic irradiation

Scdiosia patients

111221

Hcdgkin's disease (Slanfad) [I121

SlnrtalilyLife span study [ R Z ]Agc at exposure
X m e since cxposure

c20 ycan>20 ycars
5-19 years
20-29 years
30-42 years

All
Canada TB t l w r c a q y [M 191 '

"

34
70
35
26
43

13.0
61.1
28.7
20.7
24.2

0.28
0.27
0.26
0.27
0.27

303,'m428,100
338,258
194.149198.925

5.69 (3.2-9)
0.55 (~4.2-1.5)
0.80
0.92
287

244 (1.4-3.7)
0.78 (<4.3-21)
0.68
0.99
3.49

104

74.1

0.27

731.300

1.79 (0.6-2.1)

1.81 (0.621)

212

157.5

0.43

2823000.81 (03-1.2)

4.52 (2.66.6)

90% a in parenthcses derived han published data for ~ h lifc
c span study and using exact Pcisson methods for thc a h c r studies.
For cohort studies thc numbers d observed and c x p a c d caws as udi as thc mean d m e and person-ynrs arc computcd for e x p d petsons mly.
Excess absolute risk d mblcal c a n m is computed u i n g baseline incidence data dmved f r a n the cohort study [B12].

Populatiavexporcduchildren.
Original model included a fador to allow fa diflhcnccs bctwccn Sma S d i a and a h e r Canadian prmincrs. The computatim &the expeaal numba dcascs
includes an allowance f a this c K d .

UNSCEAR 19% REPORT110PART IX: BLADDER

WY

Obwd

Expecrcd

cues

Caw9

Mean dUFE(St9Persony cars

Avaagc excess
reIari,r rkk(sv-I) a

A w a g e ccras
duolute r i d '(lo' PYSV~'Incidence
Life span sndy [TI51
Male
Fcmale<20 years>20 years

S u

Age at cxpoourc
All
Cervical cancer core-trol

[B21]

76
39
12
103

70.3
27.9
10.3
87.6

0.23
0.22
0.23
0.22

297,500
491,200
363,300
425,300

0.35
1.80
0.71
0.79

0.61
1.02
0.20
1.62

115

98.1

0.23

788,MX)

0.76 (0.3-2.1)

0.95 (0.3-2.1)

273

65.6

45

n.0.

0.07 (0.02-0.2)

0.12 (0.04-0.3)

Afortality
Life span s l d y IR23j
Scx

Male

M

Fmalc

24
5
55

26.9
20.0
1.8
45.1

0.23
0.23
0.23
0.22

471.800
731,300
574,SOO
~XW'J

1.45
0.88
7.43
0.99

0.83
0.24
0.24
0.71

60

16.9

0.23

1,203,100

1.22(0.3-3.3)

0.48(0.1-0.9)

Ankylaing qmdylitis [W.
L6]

20

16.7

1.45

130,616

0.14 (-0.1-0.5)

0.17 (-0.2-0.6)

Benip gynwcdogical dixase [IS]

19

9.0

6.00

77,8780.19 (0.10.3)

0.21 (0.10.4)

Mevopalhia hacmorrhagia ID231

20

6.7

5.20

47,1440.39 (0.2-0.6)

0.54 (0.30.9)

A@ at exposure<20 years
w20 ycanAll'

90% Cl in parenthescz dcrivcd from published data for the life span study and using exact Poisson mcthods for the dher sldicr.
The excess absdulc riak cstimatc was computed using badcground incidence ratcs eslimatcd using the cervical cancer c o h a l sludy [B12j.

PART X: BRAIN Ah?) CENIRAL NERVOUS SYS'IXM

w')"

Atwage a c o sduolurc r k k '(10'PYSV).J

307, 100
509,300
376,100
410,200

-0.30
0.46
1.05
-0.03

-0.21
0.43
0.44
-0.03

0.26

816,300

0.22 (4-1.3)

0.18 (cW.6)

6.4

1.5

283,930

4.08 (3.1-5.2)

1.21 (0.9-15)

8

1.4

1.4

48.1 15

3.37 (1.34.7)

0.98 (0.4-1.9)

16

17.1

0.1

379,283<-0.2 (~-0.2-4.2)~ - 0 . 1(<-2-1.5)

48 7.200
757,900
601,M)O
757.900

0.03
3.05
0.67
1.95

0.01
0.67
0.13
0.68

OlutndExpecEr

Mean d o ~ e

cares

cme~

(SV)

l'asonyears

51

21.7
453
15.7
51.4

0.27
0.26
0.26
0.26

71

67.1

krdi rinca apitis [It lo]

60

New Yak tinca capitis [AllSkin hunangioma IF121

S ~ Y

Atwagc u c u s
rclaritr risk

Incidence
Lilc span study [TI51

Sex

Male
Female<20 years>20 years

Age at exposre
All

2ll
51

Jo

XIorIalilyLife span study [R23]
Sex

.Male
17cmalc<20 y a m
>20 years

Age at expmure
AllAnkylosing spmdylilis[D6, L6l

Pituitary adcnoma (UK) [B9]

16
28
14
32

22.4

0.27
0.26
0.26
0.26

45

39.7

0.26

1.203,lOc)

0.52 (c0-2)

0.17 (c0-0.5)

22

14.0

0.14

130,616

4.06 (0.44.9)

4.36 (0.5-9.5)

5

0.5

45.0

3760

0.19 (0.1-0.4)

0.26 (0.1-0.6)

17.9
16.6
12.1

90% a in parenthcscs dcrivcd f r a n published d a ~ afor the life span study and using exact Poisson mclhods for ~ h ua h a s ~ u d i n .
Exdudes tunours d the spinal cord.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

111

PART XI: THYROID ISCIDESCE

Sudy

Life span study [TI51
Sex
Age at cxpmurc

Male
Female0-9 years
10-19 years
20-29 years>20 years>30 years

All
Tuberculosis, adeniris screening
Agc at exposure<20 yepn
FQ S611>20 yeanAswage a c a s
relarite risk

A w a g e mas
a b s ~ / u r crisk 'Ohraved

EqPcrrai

M a n dare

Cases

cme

(Sv)

Pcrsonyems

22

55

14.9
79.4
7.6
14.6
175
67.1
53.5

0.27
0.26
0.21
0.31
0.28
0.26
0.25

307,167510.388
185,507
I9QO87132738442,000
309,224

1.80
1.49
10.25
4.50
0.10
0.3 (~-0.2-1.2)
0.04

0.87
232
4.21
3.46
0.13
0.5 (43-1.9)
0.06

132

943

0.26

817.600

1.5 (0.5-21)

1.8 (0.8-25)

6
2

0.0
0.2

6.20
8.20

950
3,100

36.5 (16-72)
1.2 (0.1-3.7)

7.7 (3.3-l5)
0.7 (0.1-24)

110
24
35
18

n

(sv") "

(1

0'PYSV).~

Cohort studies in children

l i f e span study [TlS]

45s

59

22.2

0.26

375,600

6.3 (5.1-10.1)

3.8 (27-5.4)

Isradi tinca capitis [Rm

43

10.7

0.1

274.180

u (2347)

13 (9.0-18)

New Y a k tinea capitis IS611

2

1.4

0.1

79.m

7.7 (4-60)

1.3 (4-103)

37

27

1.4

85.2M

9.5 (6.9-12.7)

3.0 (22-4.0)

Childhood cancer ITS]

23

0.4

12.5

50,6094.5 (3.1-6.4)

0.4 (0.2-0.5)

Skin haanangioma [Flf F15J

14

7.1

0.23

n.a.

4.2 (0.1-29)

n.a.

up-

0-19 years

Rochesta thymic irradiation

IS541

Scrrtning studies in children
Lymphoid hyperplosin sacening[P8 S61]

13

5.4

0.24

34.7005.9 (1.8-11.8)

9.1 (27-18.3)

Thymus adenitis saecning [MZS61j

16

1.1

290

44,3104.5 (27-7.0)

1.2 (0.7-1.8)

Michad R a e , tonsils 8 [S63]

309

110.4

0.60

88,1013.0 (26-3.5)

37.6 (32-43)

11

0.2

4 9

6.800

12.0 (6.6-20)

3.5 (20-5.9)

T&lhhymur/acnefsaecning [DlE. S61]

Studies in adults

Gmd canar c a x a n t r d ' [BZl]
G n i c d c a n ~ c r c o h ~ ~ [Bll]
~

43
16

16.8
12.5

0.11
0.11

n.a.
342786123 (~070.0)
2 5 (d4.8)

5.8 (4-32.9)
0.9 ( 4 - 2 5 )StanFord thyroid [I161

6

0.4

45.0

17.7000.3 (0.1-0.7)

0.07 (0.03-0.1)

W m Cl in parentheses dmvcd f r a n published dab f a the life span snrdy and using exact Poisson methods for the aha m d i a .
Doses lo the thyroid in this study may be much more uncertain lhan dows to agans dircaly in the x-ray beam.
E.xpccted numbcr d caws mcnputed using e x c u r rdativc risk cuimatcs dvcn in [Sbl].
hn d m . P a m - y c a r s and u p x e d number d cascs estimated f r a n data given in [S61].
B;uod rn cchon members uith 15 a more y e a s d f d l w - u p and population expected rates for non-mdanana s h n tumturs of the h a d and neck r u m .
This was a study of ncdular disease and cancer cases were not omfirmed.
Study indudes no uncxpod contrds; u t i m a t a d the number of expected cam were canpuled using Ihe fitted excess rdatiw risk rcpatcd in [S63]. Resulu
arc bawd on the new dosimetry described in [S63]. 7 h e large exa b d u r c risk in chis study illustratu the impact d succning on thyroid can- risk
cstimatcs. As described in [S63]. a special thyroid s c r c e ~ n programmegin this cohofl u a s initiated in 1974. This screening led to a largc inaeasc in thc number
d i n a d m t cases detected among both cascs and ccnuds. The papa describcc an analjsis in uhich allouance u a r made f a the cffea of screening The
screening-adjusted exabsolute risk was estimated as 1.7 (10' PYG~)-'.
Excludes cases diagnoacd during first 10 years d follow-up.

UNSCEAR 1994 REPORT112

PART XII: ELJKAEMIA

OhsendExpertrd

Meun dose

cares

cu.3

(SV)

Personyears

33

353
32.1
17.9
49.5
5.1
40.3
16.5
28.1

0.26
0.25
0.26
0.2s
0.25
0.25
0.25
0.25

141

67.4

141

C - ~ ~ l d h ocancerd[TT]

Average a c e s
relotire risk

.Jwagc a c a s(sv-l)aahsolute rick '(1o4 PYSVJ-I

412,300
664,500
478,100
598,700
160,900
367,200
277,900
270,800

3.91
4.75
6.11
3.70
18.69
0.46
3.32
0.70

3.31
229
228
3.4
5.87
0.50
221
0.72

0.25

1,076,800

4.37 (3.2-5.6)

273 (2.0-3s)

ma.

7.20

n.a.

0.74 (0.1-3.8)

0.50 (0.1-2.6)

25.

ha.

10.00

n.a.

0.00 (O.OO00.m)n.a.

Breast cancer therapy [C2J]

38

n.a.

7.50

n.a.

0.19 (0.00-0.6)

0.89 (0.00-3.0)

T d a Rivcr pcpulation F I E ]

37

19.3

0.50

388,880

1.84 (0.9-3.1)

0.91 (0.4-15)

Y ~ Y

IncidenceL f e span study [P33]Sex
A@ at exposurel i m e since exposure

Male
Fcmalec20 years>?O years
5-10 years
11-20 years
21-30 years
31-42 years

Al I

Centcal cancer case-eontrol

lB21]

71
70
46

95
29
45
34

hfot-lality"'fAnkylosing spmdylitis [D6,L61

36

11.9

3.83

165,758

0.53 (034.6)

0.38 (0.2-0.6)

lsrncli tinea capitis [RYJ

14

6.0

0.30

279,901

4.44 (1.74.7)

0.95 (0.4-1.9)

Benign g)namlo@cal hseasc [I121

47

27.6

1.19

246,8212.97 (2.2-4.0)

1.25 (0.9-1.7)

Massachusetts ?B fluoroscopy [Dl41

17

18.0

0.0')

157,578c-0.2 (~-0.2-4.5)

c-0.2 (4.2-5.1)

Peptic ulcer [Gllj

8

29

1.55

35,815

1.13 (0.4-2.5)

0.92 (0.3-2.0)

Metropatha hammhagica [D23]

12

5.6

1.30

53,1440.84 (0.3-1.9)

0.93 (0.3-2.0)

90% CI in parentheses derived from published data for the life span study and using exaa Poisson methods for the other studies.
CIS for the cervical cancer data m exrelative risk were estimated from the confidence reicm curved in p421; the excess absolute risk &mate used
incidenm cstimatcs from the c o h a t study P I ? ] .
Risk estimates based on an unmatched analysis of data @ven In ITS].
The excess a b d u t e risk f a this study is computed based on annual incidence estimates and average follow-up Gmes reporled in [as].
Areestimate of the dcse to b m e marrow in this study indicates a mean dose of 0.60 rather than 0.30. Consequently the cxccss rdative risk becomes 222 Pn].
Excludes cases of chronic lymphocytic leukacmia.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

113

PART XI11: NON-HODGKLV'SLYMPHOMA

scud>.

0brm.dExpcrrd

cares

casm

M ~ M
dare
(SvJ

Pason-

yens

Atwagc a c o s
rduriw risk
(SV-', aA ~ w a g ea c 6 sabsolute risk '1(0'PYSI~-~

Incidence
Life span study [P33]Sex

AF at exposure

Male
Female<20 yeus>20 yeanAll

Grvical cancer raw-cmhol

[BZl]

41
35
17
59

33.2
383
15.8
55.7

0.26
0.25
0.26
0.25

412,400
664,500
47a 100
59&600

0.91
4.34
0.30
0.24

0.73
4.20
0.10
0.22

76

715

0.25

1.076.900

0.25 (~4.2-L1)

0.17 (<4.34.8)

94

aa.

7.10

n.a.

0.21 (0.1-1.1)

0.04 (0.024.2)

bfortality
Ankyloring rpmdylitis [D6.L6]

16

7.1

3.83

130,6160.32 (0.14.6)

0.18 (0.14.3)&nrpgynamlogcal disease PI21

40

42.5

1.19

246,8214.05 (<-0.20.2)

4.08 (c-0.34.3)

Masrachuats TI3 fluoroscopy [Dl41

13

13.1

0.09

157,578

4.05 (<4.2-6.5)

4.04 (4.2-5.4)

Peptic ulcer (GI11

12

6.4

1.55

35.8150.57 (0.1-13)

1.01 (0.1-24)

4

5.3

1.30

47.1444.19 ( ~ 4 . 2 4 . 6 )4.22 (e4.24.6)- Metropatha hannorrhagica [DZ]"

90% CI in parentheses derived From published data for the life span srudy and dsing exact Passon methods for the ah- srudies.
as for the m r i d cancer dam m ex- relative risk were cnimatcd from Its confidence r c g m curves in [B42]; the ex- a W u t e risk atimate usa
incidence ertimatcr &om chc w h a t study p l l ] .

PART XIV: MLTLTlPLE MYELOMA

9 d y

O h s dExpcaed

Cases

cares

Mean dose

Persony cars

Avaage excess
rdarive risk
(sv-1) "Average a c r s s
obsolvrc ruk '( l f l pvsvj-'

Incidence
Life span study [P33]Su
Age at exposure

Male
Femalec20 yean>20 yearsAll
G r G d can=case-control

[B21]

12
18

26

9.2
193
3.1
25.4

0.26
0.25
0.26
0.25

412400664.500
478.100
598.600

1.17
4.28
107
0.09

0.26
4.08
0.07
0.04

30

28.6

0.25

1,076,900

0.20 (c4.2-1.7)

0.05 ( ~ 4 . 0 5 4 . 4 )

56

n.a.

7.10

n.a.

4.10 ( ~ 4 . 1 4 . 1 )4.01 (~4.03-0.02)

4hlortality*

Ankylosing spandylids [W. L6]

8

4.7

3.83

130,6160.19 (<0.040.5)

0.07 (~4.01-0.2)

Bcnign g y n a e c o l o ~ ddisease [I121

14

12.4

1.19

246,8210.11 (c0.20.6)

0.05 (<4.143)

Pcptic ulcn [GI I]

3

3.1

1.55

35.8154.02 (~4.2-1.0)

4.02 (<4.24.8)

Mecropaha hxmmrhadca [DU]

9

3.5

1.30

47.144

1.23 (03-27)

0.90 (0.2-2.0)

90% a in parenthesg dmvcd from published data for the life span study and using exaa Passon methods for the aher studita
The excess atsdutc risk estimate was computed using background incidence r a m cstirnatcd from the cerical cancer cohoti srudy [B12].

UNSCEAR 19% REPORT114

Table 9Sex-speclflc risk estimates for cancer incidence and mortality from the Life Span Study
Abwage a c a s
relabu &k(svol)

cancerppe~emala~ d e sAtwogc a c e sabsolu~erisk(lo4 PYSVJ-I,uab

Sa ratio~maicr

NOM/ Cancer
incidence

AtWOgCabirolure risk
(1o4 PYSV).~(Female :male)W a l e :f d e )

245
259
6.63
4.33
0.55
0.18
5.78
0.96
5.14
0.88
0.56

1.82
1.39
0.59
225
0.38
0.08
218
0.81
1.21
281
0.32

1.36
1.85
6.64
1.94
1.35
243
285
0.86
3.60
0.29
1.25

1.21
4.37
4.24

0.68
4.27
4.31

1.76

2.77
242
209
2.19
0.05
0.67
9.80
0.26
0.64

1.81
1.32
0.31
1.11
0.01
0.32
4.05
0.13
0.31

1.a
1.82
6.39
1.84
1.35
202
256
1.69
1.82

AVffOgea c e s
risk
(SVJJ
(Female ;mole)

Incidence 1938-198'7 IT151
All sdid t u m w s
Nmlcx spaific solid rumours
Oesophagus

Stomach

&la,
Liwr
b g

Skin
BladdaIhyroidB m c and mnnenivc tissue

0.33
0.34
0.16
0.12
0.87
0.61
0.36
0.92
0.35
221
1.78

18.96
18.89
0.41
261
266
3.09
267
0.89
0.81
0.99
0.38

0.81
0.88
1.06
0.52
0.48
0.11
208
0.88
1.80
1.94
0.99

34.44
26.19
0.24
5.86
1.01
0.24
5.81
0.72
1.02
2.78
0.12

Incidence 1950-198'7IP331

4.75
4.34
4.28

3.9 1
0.91
.1.17

Leubemi a
Nm-Hcdgkin's lymphoma
Myeloma

3.35
0.73
0.26

2.29
420
4.08

hloitality 1950-1987 [it231

All solid turncurs
Nm-sex specific wlid turncurs
Oesophagus
Stomach&Ion
Lira

Bladder
Bone nnd wnneaive tissue

0.72
0.60
0.94
0.35
0.03
0.33

0.26
0.25
0.45
0.16
0.66
0.49
0.20
1.59
1.26

1.96

0.41
0.81

8.74
7.90
0.71
201
0.82
206
0.96
0.93
0.29

15.81
10.45
0.22
2.26
0.03
0.66
3.89
0.12
0.09

Table 10
Risk estimates for cancers other than leukaemia in relation Lo age at exposureLife SPM sh&
Borh s a a

Age ar a p a s w c

0 ~ 4

0-15
15-24
25-34
35-44
45-54
>55

Ankylosing spondylirir 1061

morroli [R23]

Mainly m l c r

hiolales only

Excess relaritc
risk(sv'l)

Excess ahsolwe
risk(10'PYSI.)-~

Excess reloriterirk(SV-])

Excss absolurc
rirk(10' PYSLI-I

0.95
0.74
0.56
0.42
0.31
0.23

3.72
8.39
14.40
19.35
21.85
22.84

0.66
0.52
0.39
0.30
0.24
0.18

272
6.71
13.85
19.24
21.98
23.72

I.Yv-~)

Exces a b s o l ~ erisk(lo4 PYSI.)-~

0.20
0.12
0.14
0.17
0.08

1.67
241
6.06
12.75
8.21

Excess relorite

rirk

ANNEX A: EPIDEMIOMGICAL STUDIES OF RADIATION CARCINOGENESIS

115

Table 11
Exoess relative risk estimates for breast cancer in various cohorts in relation to age at exposum
E.uess rdntiu risk (SV-I)for age a a p a r r ~ e'S ~ YLife q m study [TlS]

10-19
yews

20-2J
yews

25-29

yws

yws

30.34
years

35-39
years

3.4 (58)

2 5 (141)

1.3 (77)

1.4 (54)

1.2 (58)

1.4 (49)

0-9

45-49

w50

yws

years

ycnrs

0.7 (92)

Massachusetts TB fluoroscopy 10311

0.7 (71)

0.5 (102)0.2 (31)(12 (13)

Cnruda lB fluoracopy MI91
Nova Scuia
Other p r o a n c u

1.9 (14)0.4 (48)

1.6 (47)
0.4 (233)

0.8 (8)0.2 (73)0 (4)0 (5s)New Y a k acute post-partum mastitis~ 9 1

0.4 (33)

Swcdirh benip breast [Bl]

0.4 (44)

0.6 (43)

1.9 (18)

2 5 (1s)

Hodgldn's dkasc [HZ]

0.4 (28)

Numbcrs in paren-

0.1 (20)

0.4 (9)0.9 (4)0.1 (7)0.1 (Z)

Contralataal beast [B18]a40-40.2 (78)

0.0 (128)

arc numkrs of cascs invdvcd.

Table 12
Excess relative risk for thyroid cancer in various cohorts in relation to age at exposure
Excess rdarivt- risk ( ~ ford )age lu apasure
savfy
c1

1-4
years

Yew

Life span study [TlS]

10-14
yews

9.5

I s r d i dnea capitrs [RlS)
Lradi-born
Nm-Isneli-ban

M~chadR a s e !cad1 irradiation [S63]

5-9
yews

3.0

20.0
67.0
3.6

7.0
27.0
28

1.4

15-19

20-39

yeas

yews

>40
yews

0.3

-0.2

UNSCEAR 1994 REPORT

116

Table 13
Estimated relative risk of cancer mortality per sievert weighted dose (RRE for neutrons = 10)
in the life span study cohort a~ 7 1
Age ur a p n r w eSa

C a n c n typec10 years

10-19 years

20-29 years

30-39 years

a40 years

LNkacmia

Male
Female

17.9
18.8

4.8
5.0

5.9
6.2

4.5
4.7

3.9
4.0

All cxccpt leukacmia

Male
Female

1.96
292

1.60
220

1.52

2.W

1.23
1.45

1.16
1.32

StnnachMale
Female

1.40
1.83

1.71
247

1.65
236

1.09
1.19

1.09
1.20

Female breast

Female

2%

289

I.%

209

1.03

Colm

Male
Fmdc

5.93

1.08
1.31

1.22
1.84

1.32
219

Malc
Female

3.82
8.09

1.39
1.97

1.67
267

1.17
1.42

1.78

Table 14
Studies of obstclric x-ray examinations in relation to childhood cancrr (Including leubemia) a
[B22]

Srudy

Oxford survey of childhood cancers
1975 [ED]1987 [K6, M22j
Renatal xqay examinations, United Stnter [M9jInter r c g i d cpidcmidogical study d childhood cancer [ H a ]Los Angela F16j
Ladriana [F13]
Hdsinki [S36]
California [K13]Tri-state [G14j
Minnesota [A81FdnbmgNLmdm [CIS]
Baltimore [Dlbj
Connecticut tuins [I131
Xcw Zcaland [GlS)
AU ahcrs
Total

Per cat!
of rorolRela~iver i ~ kinfarmmion

434.2
8120
114.7
39.0
23.9
18.3
17.9
16.6
16.6
10.2
9.0
8.3
5.4
5.4
14.3

39.1
73.0
10.3
3.5
22
1.6
1.6
1.5
1.5
0.92
0.81
0.75
0.49
0.49
1.3

1.41
1.40
1.47
1.23
1.34
1.70
1.18
1.48
1.40
1.28
0.86

l.111.6

100

1.39 '

LinirJ ofesrimare

l.M
1.83
1.13

Comments

RR: 1.94 [Mj.
-1.4 [M22]
Weighting d matched estimates
Lcukaemia d y

Lculucmia only
Lul;.cmia only
Lculuemia only; cohm study
Cohat study
RR adjusted for birth weight = 2.4
Lculucmia only

The mcasurc d information is the rcciproel of the variance ofthe log lelarive risk.
Unadjusted unlcss othcruix staled.
Based m deaths in I'ngland, Wales and Scotland, but not indudng cascs in the lnlcrrcgional cpidcrnidogical study of childhad cancer.
A study d incidcnl cascs in north and central England.
9 5 2 CI: (1.31-1.47).

ANNEX A. EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

117

Table 15
Estimated excess absolute rlsk of Incidence of all cancers over ages 0-14 years associated withprenatal x-ray exaniinialions in the Oxford survey of childhood cancers

[M221
7

Excess absolurc risk (lo4 Gy0') bared on
Y e n of b h h

DCUILFduring 19M-1979
n1h adjwrmenr
fapregnancy i l h e s u i and drugs

Deaths during 1953-I9t9
with no cdjusrnunf
for pregnnncy illnrsscr and drugs a

1946
1952
199
1962

203
100
49
27

185 (98-304)
96 (50-152)
56 (21-98)
36 (6-73)

Table 16
Estimated excess ahsolute risk for all cancers except leukaemia in the life span study cohort
In31

O'

Excess absolvrc risk ' (I PYSL~J.'
Agc al aposurc

0-19ycars
20-34years
a35 years

Followup rime 19561%5

F d l o w u p lime 1%6-1975

F d l o w u p I L K 19761985

0.083
0.40
0.35

0.31
0.79
1.4

0.73
1.6
3.5

" Estimates arc for males. 'The corresponding n l u c s f a females are obtaincd by multiplying by a factor 1.56

Table 17
Estimated relative risk of mortality for ranges of absorbed dose above and below 2.0 Gy in the llfe span study
cohort a[S'I
Orgcn a h &*dare (Gy)of C M C C ?

0.01 -0.05
All cancers
except larlcaania

Larkaunia
St~machLung
Female breast
Cdm

0.06-0.09

0.10-0.1 9

0.20-0.19

0.50-0.99

1.00-1.99

1.06 (1.0-1.12) 1.08 (0.98-1.19) 1.06 (0.97-1.16) 1.12 (1.03-1.21) 1.36 (1.23-1.51) 1.66 (1.45-1.90)
0.99 (0.68-1.40) 0.61 (0.25-1.22) 1.08 (0.61-1.62) 1.79 (1.18-2.66) 4.15 (2.76-6.19) 8.01 (5.34-11.9)
1.06 (0.96-1.16) 0.93 (0.78-1.10) 1.05 (0.90-1.22) 1.16 (1.02-1.32) 1.28 (1.07-1.53) 1.29 (0.99-1.64)
1.30 (1.11-1.54) 1.21 (0.89-1.62) 1.02 (0.75-1.36) 1.54 (1.22-1.93) 1.63 (1.19-2.19) 245 (1.73-3.38)
1.12 (0.601.59) 1.02 (0.49-1.89) 1.10 (0.60-1.89) 1.39 (0.85-2.21) 267 (1.62-4.27) 239 (1.09-4.59)
1.04 (0.80-1.37) 1.01 (0.61-1.59) 0.53 (0.29-0.91) 0.93 (0.60-138) 1.04 (056-1.76) 223 (1.20-3.81)" DS86 dosimetry, both cities, both sexes, all ages at exposurr, 1950-1985;comparison is uith the contrd (0 Gy) goup.
90% CI gi-

in parcnlhcses.

a 2.00205 (1.66-2.50)
18.6 (121-28.2)
1.73 (1.19-2.43)
214 (1.16-3.59)
4.22 (1.77-8.54)
5.87 (3.02-10.3)

UNSCEAR 1994 KIiPQKT

118

Table 18
Adjusted and nued relative risk of thyroid turnours among lsraeli children irradiated for tinea capitis api151
Malitnanr r w n ~ s

Benign hunours

Ahorbod dacein rlryroid (GY)

00.04407 (mean dole 0.062)
0.08-0.14 (mean dosc 0.102)
0.15-0.50 (mean dole 0.214)

"

Ohsd

Person-

cares

yems

16

412,030
106.690
149.?20
17,TIOl5
24
4Rdnrivr risk

OhsoyadPerson-.

R d h u risk

A d j dFilledcaves

yws

A d j d b

FinedC

1.0
3.3
4.2
6.1

1.0
3.0
4.3
8.0

41
17
32
6

316.840
82.350114,930
12,840

1.0
1.1
3.0
4.5

1.0
1.9
24
4.0

Considerable uncatainty may edst in the estimata of dme to the thyroid gland.
Adjusted f a K* ethnic a i g i n a d attained agF.
AEsuming a linear inncase in relative risk uith i n a u s i n g d a c .

Table 19
Cancer incidence and risks of breast cancer among women wilh tuberculosis given c h a t x-ray fluoroscopy
[B311

*

Based on maximum l i k d i h d m a h o b t o mmpute rdjustcd risk atirnates d the ratio obsaved/expeaed mlues between expaed and aoaadjustingfor di£fermca in backgrcund rater betweca sukohorcr. E x m r risk also dnived frcm this approach.
Rttcd relative risk and fitted excess risk in parenth-.
Bued oo bat-fitting linear doc-response model accounting f a agc, calendar year, followup andsubcohort.
p < 0.05 (me-rided).
For u;portd indiGdualr with known dose ( e x d u d a 0 lad unbnma dme).

Table 20
Evaluation of various dose-response models for breast cancer incidence among women wilh luberculosis given
chest x-ray ~ U O ~ C O ~ Y

Modd

*

M

~

k opr&nd'

PrpameferF^trLMlc*

95% CID n k c difcraur

LinearI = a,&mc (1 + .ID)

a1

0.7 1

(0.40-1.08)

0.26

Quadratic

I = %&timc (1 + a z ~ ?

az

0.22

(0.10-0.41)

6.29

Iinearquadratic

I = o,&~,,,~ ( 1 + alD + .a$?

0.85
-0.07

(0.19-1.73)(-0.28-0.21)

0.00

a2

1 d m d e s h e a s cancer inadena. D denotes b r a t dole (cGy). lag+&= d m t e s background parameter adjusted f a age d timc The model also i n d u d a amultiplicative age-at-aporure effect m the e x m s rdatiw risk ( n d r h ) .
Based on there model& the estimated RRs f a a P y e u d d e x p d to 1 Gy are 1.70, 1.22 and 1.81 for the linear, quadratic lad li~earquadraticrnoddr.
respeaivdy.
The dcriana is a measure of unexplained variance wcd to a m Mess offit of different nested models. The deaance d i K a c n m are baareen the indicatedmodel and the linearquadratic model. l k i s difference a n be interpctd a, a single degree-of-frcedorn X2 statistic of the adequacy of the drnpln method. ?heresults indicate that the linear model describes these data as well as the linearquadratic model (p > 0.5), but that the pure quadratic model docs not fit well
@ = 0.01).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARClNOGENESIS

119

Table 21
Dose fractionation efrects in thyroid caners among individuals in Rochester, New York, given x-ray treatment
In infancy for supposed enlarged thymuses a
(S101
-

R&h!

C~WQCC&IKS

Mean rod dare

ICY)

Pason-years

ohr~rdOcrss ahsalure ript
(lo' P Y G ~ ) - ~N w b u of ranctrs

Dore p a bation (Gy)0.014.49
0.50-1.99

0.18

34,268

4

6.1

222

&an

2.0-5.99

3.14

14,340

6
12

22
23

N u m k c€ d a e frndjms
1

0.74

29,414?2,417
5,44 5

7

6

29
1.5

9

3.8

0.74
1.41

29,334

7

13,8965

207

13,980

10

29
24
1-9

2

1.55

3

254

Avuage i n t d
0 days

1 4 &)a>4 days'

lreamcots

Data shown u e fa individuals with iaal thyroid doses d Icu than 6 Gy.
F.xces in canparism to connd group rstq uith adjustment by sex ethnicity and interval s i n e irradiatim to the -tinedchc m d group.

distributim d these goups plus

UNSCEAR 1994 REPORT

120

Table 22
Summary of studies or nicdlcnl personnel exposed to radiation showing cancer types
with significantly (p < 0.005) increased risks[a1
NumberWY
Mortality in male ndidogius(United Kingdan) [S38]pcr='nr

WY
pcra

t338

1897-1954o/Period ofsubgroup

RdaivrCanca types in ercess=My

Pre-1921

All
Pancreas
Skin
Lakacmia

Mutality in male mdidogim(United States) [M24]

Cancer inadence in Chinese
x-ray workers [W141

M c d i t y in Japanese ndidogicaltecbndogists [A91

Can= i n a d a c e in Danish
radiolhsapistr [E7]

"

6524

27,011

9.179

4.281

1920-1969

1950-1985

1969-1986

1954-1982'&k

Number

of

L(

cm.5

1.41
3.23
218
7.79
6.15

64

6
8
6
4

1920-1954

No cancers differed significantly haa expatation in chis
subgrcup but canca mutality increased significantly aithtime since cntry to the study

1920-1939

All
M w t h and pharynx
Liver (sccoodary)
Skin
Unapxified sites
h e leukacmia
Myeloid l e u h a n i a
Lymphosarcana

1.38
217
3.22
3.38
1.69
223
239
273

1940-1969All
Mwth and pharynx
Lug
Multiple myeloma

1.15
288
205

Pre-1961)

All
Ocsophn ys
Liver
Skin
LeuLaemia

1.3
5.5
1.8
29
26

193
13
37
7
17

1960-1969

All
liver
Skin
Lcukacmia

1.3
22
1.6
3.0

90

1970-1985

All
Oesophagus
Liver
Skin
Leukacmia

0.8
3.8
1.2
4.8
1.3

49
2
8
1
4

1969-1982'

All
Large intestine
Neuroccrebnl

1.32
222
8.I6

137
20

1983-1986

Leukaernia
Other

183
1.92

7
27

a10 years

All
Prostate

1.13
6.25

103
4

Adjund fa age and paiod.
b a e d death calculated using rates in social d a s r I males; RR = 1.n using rates in male medical practitioners.
P a i d d obacrvatim.
All malignant ncoplasrns other than ocsophagur, stomach liver, pancreas, lung and Icukaemia.
Provisional results available only to 1984.

1.22

20
1

13

4

ANNEX A: EPIDEMIOMGICAL STUDIES OF RADIATION CARCINOGENESIS

121

Table 23
Cancer incidence in diagnostic x-ray workers in China
P141
L&

All cancers ace# leukaemia
Age at f i
anploynvnr

Woid c a n c oBrearr CMCC

Ohsmvd
Nunbe

Rate
ratio

OhFawdnumber

Rate
raw

Ohmad

Rate
raw

O h s dnumbernumberRate
ratio

c20 years
20-24 years
25-29 years
3-34 years
35-39years
240 yuus

24
70
91
60
28
25

1.5
1.1
1.3
1.3
0.9
0.8

5
15
8
5
1
0

5.9
4.1
1.9
0.6
0.0

0
6
10
4
0
0

0.0
1.4
3.3
1.6
0.0
0.0

2
3
2
1
0
0

5.4
20
1.6
1.2
0.0
0.0

All ages

298

1.1

34

2.4

20

1.5

8

1.7

2.2

Table 24
Parameter estlmaks from the life span study used in lifetin~erisk computations a
Moles

Females

Sire
Exems rclarivr risk

(sv-')='-i"'alP
Stomach61m

Livrr
BladdcrBreastWY
Otha

All solid tumcurs

Age-atapnswc fleer

0.23
0.16
0.54
0.97
0.37
1.00

0.015
0.035
-0.033-0.027
O.M1
0.012

0.59
0.45

Exccrs relarive risk
(5-1)

Age-at-aparurc Lffecr

0.059

1.59
0.62
1.00
0.32
1.06
1.19
1.95
1.42
0.39

0.015
0.035
0.033
-0.027
0.021
0.012
0.079
0.042
-0.059-0.026

0.77

0.026

The paramaas are a (excess relative risk per sievcrt) and b (agear-exposure effect) in the model ERR0.c) = aD exp [b(e - 91, whne D is the weighted
dose in intestines (RBE for neutronr = 10) and e is the age at exparwe.

U N S C W 1994 REPORT

122

Table 25
Estimata of excess relative risk per slevert lor solid tumours based on fits to dnta of Ule lire span study a

Excess relafive rbk (SV-')F a mala ru age of orpanucc

Sire

F a females at axe of aposure

10 years

30 yews

50 yems

10 years

30 years

50 yeas

0.18
0.27
0.90
1.45
o.n
0.83

0.2s
0.13
0.46
0.85
0.41
1.06

0.34
0.07
0.23
0.49
0.63
1.36

1.43

0.44

au

1.n
0.52
0.84
0.28
1.17
1.n
1.32
1.15
0.29

234
0.26
0.43
0.16

oha

1.26
1.05
1.64
0.48
0.78
0.99
6.38
264
0.95

All d i d h n w r

0.66

0.40

0.23

1.14

0.68

OaophagStomach
Colm
Liva

Lung
Bladda
&art
Chary

1.n
162
o.n
0.50

a09
0.40

'Ibc puunam and modd are presented in Table 24 and its footrmc.

Table 26
Estimates of excess absolute risk lor leukaemia for acute exposures of 0.2 Sv and 1 Sv of low-LET radiaUon
bttsed on fits to data of the life span study a[P331
Etcers absolure risk for males (I# PYSVJ-I*

Excess abrolure r k k for females ( 1 d PYG~).'

Age a

0.2 Sv

apanve6mrsJ
5 pars20ycun

41)~.

drr

QPMVC

0-19
20-39
40

23
1.5
1.2

-we

0.18
0.21
0.43

4 0 v nr

uzmswe

0.01
0.02
0.11

1 Sv

0.2 Sv

1 Sv
Sycon

20ycnn4Oyean5 ycnn20ycnn40 yean

qR~r

3er

&er

apruwc

afler
upawe

3rr

qaxwe

q7u
PQafwe

1.4
1.6
3.3

0.05
0.12
0.82

0.62
0.41
0.34

0.22
0.26
0.53

0.05
0.14
O.%

UFUWC

17.7
11.6
9.5

an exabrdute risk model with time-. ux-and age-at-exposursdependence (see equation 14).
* Using
Dore is weighted dcse to b e manow (RBE fm ncutrais = 10).

S ~ a n#cr

2OyronU ) p n40

3~

apruwco p ~ a

4.8
3.2
23

1.7
20
3.9

0.4
1.1
8.2

Table 27
Death mtcs for selected cnuses in the populntlon of Japan, 1%5[J~I

F d r rMales
A8C
caregory(vems)

0-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
4549
50-54
55-59
6044
6549
70-74
75-79
80-84
85-89
>90

Poplarimi

Death r a t s (1 0'')Poplarion

Borh suesI)carh rates (10')

Popularinrr

Dearh rates (I@')(rhwMds),411 causcr

Lcukaania

Sdid Nmarrs(rhcusonds)

All c a v r a

LhaniaSdid tuntows(rhwands)

All c a u a

Ldaania

Sdidtumaus

3.792
4,345
5,115
4,571
4,134
3,915
4,524
5.365
4,527
4.072
3,911
3,395
2365
1.770
1.497
1,014
541
203
53

158.8
26.6
19.9
69.8
81.4
80.7
93.3
131.9
227.7
371.7
624.6
906.7
1,314.9
2,159.4
3,707.7
6,581.0
10.799.1
18,136.2
25,429.3

1.3
2.6
2.2
2.7
2.2
2.1
2.8
3.4
3.8
4.8
5.8
7.5
10.2
14.6
20.4
25.8
25.6
24.5
21.7

2.9
2.1
2.0
3.5

3,615
4,131
4,865
4,351
4,000
2,840
4.46 1
5,309
4.559
4,125
3,991
3,577
3,013
2,400
2,053
1,472
889
399
129

131.2
15.3
13.1
23.7

1.4
1.7
1.6
1.7
1.3
1.5
1.9
2.3
3.0
3.6
4.7
5.4
6.4
7.6
9.9
129
12.5
12.7
10.0

2.4
1.5
1.9
2.1

7,408
8,476
9,980
8,922
8,133
7,754
8.985
10,675
9,086
8,197
7,902
6.972
5,3n
4,174
3,549
2485
1,429
602
181

145.3
21.1
16.5
47.2

1.4
2.2
1.9
2.2

2.6
1.8
2.0
2.8
31
7.6
14.6
27.5
51.4
89.0
165.6
266.0
386.3
569.2
828.4
1,167.1
1,373.3
1,510.4
1,240.3

3.6

6.9
123
25.5
50.4
98.4
207.7
356.4
536.5
822.3
1.204.2
1,705.0
2,019.0
2,267.3
1,764.5

31.8

40.7
55.6
76.0
124.1
184.6
289.7
414.9
663.0
1.106.4
1.998.4
3,871.3
7,165.7
13,067.1
22490.8

3.2

8.3
16.9
29.5
52.4
79.9
124.2
180.3
269.2
382.1
555.4
794.3
980.2
1,142.8
1,018.4

57.1

1.8

60.9
74.5
104.2
175.6
277.1
455.6
654.3
948.7
1,554.02717.54.980.5
8,540.5
14,725.6
23,364.8

1.8
23
2.8
3.4
4.2
5.2
6.5
8.1
10.6
14.3
18.2
17.4
16.5
13.5

UNSCEAR 19W REPORT

124

Table 28
Canpadim of measum of Hfdlme rkk d m o d i t y fnw solid tumours foOowing acute whde-body q u r e o f 1 Sv a

A t e ar apasurc(v-SJ

Risk o/ aparure-induced dearh (REID)

E x m s life~imcrisk (ELR)

(%)

(%)

10
30

17.0
9.3
7.0
28

145
8.1
6.4
26

50
70

Estimates were mmprned using sex- and age-et~xporurc-lpedfic relativerisks estimated f a the life span study a n o n m d i t y data for the period 1950-1987.
Risks were applied to 1985 death n t a in Japan [JS]. Since sa-specific cstimatea of Ihe excess risk w a e drlually identical, the a t i n u t a in this Table are
averages d both the sexes. Projcdim beyard the followup period ssumes wnstanl relative risks.
h e is weighled dare uith neutroo RRE = 10.

-

Table 29
Estimates of lifetime risk for leukaemia following acute whole-body exposures of 0.2 Sv or 1 Sv from low-LET
radiation

Age ar apasure@ears)

Rivk ofapasurtinduced deah (REID) ('76) 'Maler

F d e rBorh

Years of life last per rase ('k7.C)

I

*
Bah

Males

Fads

67
62
58
53
46
42
37
33

64
59
54

66
60

SO

16
14
13
11
9
8
6

52
42
38
34
30
20
18
15
13
11
8
6

64
59

66
61

54
38

56
51
42

Etpoaurc d 0.2 S v 'h'oubno

5
10
IS
20

U
30
35
40
45
50
55
60
65
70

0.22
0.22
0.22
0.22
0.16
0.16
0.16
0.16
0.18
0.17
0.16
0.15
0.13
0.11
0.09

0.11
0.11
0.10
0.10
0.12
0.11
0.11
0.10
0.24
0.19
0.15
0.12
0.09
0.06
0.04

0.16
0.16
0.16
0.16
0.14
0.14
0.14
0.13
0.21
0.18
0.16
0.13
0.11
0.09
0.07

25
21
18
IS
12
9
7

38
34
30

n

56

Expw~rcd 1 Sv 'Newborn

5
10
15
a0
25
30
35
10
U
50
55
60
65
70

"

1.64
1.67
1.61
1.66
1.25
1.25
1.24
1.23
1.40
1.34
1.25
1.15
1.03
0.88
0.71

0.81
0.81
0.81
0.60
0.91
0.88
0.84
0.m
1.60
145
1.15
0.90
0.68
0.50
0.34

1.23
1.24
1.24
L23
1.08
1.06
1.04
1.01
1.60
1.39
1.20
1.03
0.86
0.69
0.53

67
63
58
53
46
42
37
33
25
21
18
15
12
9
7

50

34

3a

31

34

n

30

16
14
l3
11

20

9

8
6

18
1s
l3
10
8
6

Computed usingtirne-, sex- and agc-at-expc8ure-rpeafic e x c u r absolute risk model for the life span study leukncrnia incidence data f a 1950-1987p33]. Risks
W a c applied to Japanesc death rates of 1985 [JS].
A r a a g e years d life 1- p a exposure-indud death The average years of life lost pa cxporcd persar is cqual to y m d life lort p a care mdtiplied byrisk OE expaweinduced death divided by 100.
DOM is weight4 dose a i t h neutron RBE = 10.

125

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

Table 30
Estimates of projected lifetime risk of solid tumours following acute whole-body exposure of 0.2 Sv or 1 Sv fmm
low-LET radiation

Age m
-a

mab

Rirk of apasurcindrrced deah (REID) /%) af a projection method Hirh a J & y w latent period and r d a i v c
rhk

Yems of life lad p o caref a projection method Hirh a I&year lorcnr priod and rdnrire risk

d conctmt
from 10 years
aflm a p o s w c

Ad comrmt
from 10 years afterbears)A

Declining ro riskf a age 5 0 years
a! a p a i u r e

Declining toz a o ruka age PO yews

Declining to ruk
f a age 50 yews
a apaiure

Declining ro
w o risk
m age 90 years

14.3
14.0
13.8
13.5
13.2
l2.8
12.4
11.9
11.4
10.7
10.0
9.1
8.3
5.9
4.2

17.4
16.6
15.9
15.1
143
l3.6
12.8
121
11.5
10.7
10.0
9.1
8.3
5.9
4.2

20.2
19.7
18.9
18.1
17.1
16.0
14.7
13.5
12.3
11.2
10.0
9.1
8.3
5.9
4.2

15.3
14.8
14.4
14.0
13.6
13.1
12.7
12.1
11.6
10.9
10.1
9.2
8.4
6.0
4.3

17.9
17.1
163
155
14.7
13.9
13.1
123
11.6
10.9
10.1
9.2
8.4
6.0
4.3

20.6
20.0
19.2
18.3
17.3
16.1
14.9
13.6
12.4
11.3
10.1
9.2
8.4
6.0
4.3

e-

Exposure of 0.2 Sv '

Newbm
5
10
15
20
25
30
35
$0

45
50
55
60
65
70

5.8
4.6
3.8
3.1
26
22
20
1.8
1.6
1.5
1.5
1.4
1.3
0.8
0.6

3.5
3.1
28
25
22
20
1.9
1.7
1.6
1.5
1.5
1.4
1.3
0.8
0.6

26
22
20
1.8
1.6
1.5
1.5
1.5
i.5
1.5
1.5
1.4
L3
0.8
0.6
Exposure of I Sv 'Newborn
5
10
15
20

25
30
35
$0

45
50
55
60
65
70

"

24.9
20.6
17.0
14.2
l2.1
10.5
9.3
8.4
7.8
7.4
7.0
6.7
6.4
4.1
28

16.1
14.4
12.9
11.6
10.6
9.7
8.9
8.3
7.8
7.4
7.0
6.7
6.4
4.1
28

12.1
10.6
9.3
8.4
7.8
7.5
7.3
7.2
7.2
7.1
7.0
6.7
6.4
4.1
28

Estimated percentage d populatiat that wwld dic duc to radiation-induced cancer. Computed using sex- and age-at-exposure-specific relative risk estimatedfor the life span Sudy canccr mortality data For 1950-1987. Risks
applied to Japanese death rates of 1985 [JS]. Since sex-specific estimates of the e x m s
risk were virtually identical, thc estimates are averaged over ser
Average years d life lost per e-re-induced
death. 'lhe average years of life lost per exposed perscm is equal to years d life lost per case multiplied byrisk of exposureindueed death divided by 100.
Canstant relative risk for first 45 years afler exposure; risk then dcacascs linwrly wilh agc A! attaincd age 90 years, the risk is equal to that F a a persoo aged
50 years at exparurc.
Comtant risk for first 45 ycars after exparwe; risk then decreases linearly uith age. At anained age 90 years, the risk is zero.
Dasc is weighted dare with neutron RBE = 10.

UNSCEAR 1994 REI'OII'I'

126

Table 31
Comparison of estlmattu of lifetime rkk of mortality from solid turi~oursand leukaeliiln following acute wholebody exposures of 0.2 and 1 Sv 'Risk o/ aparure-induced deorh (RE//>) (%)
Projurion merhod

Fdlouing expasure of
0.2 SVF o l l o ~ i n gcrparwe ofl SI~)'curs of life lmf p a case M C )Fdlouing crparwc of
0.2 Sv

Fdlowing a p w e of
I Sv

10.9
9.2
7.5
9.7

11.2
12.1
13.6

11.6
123
13.3
11.4

1.1
1.0

31

31
26

Sdid tumnun*

Gatstarit rdative risk
W i n e to risk f a age at exposure 5 0
Decline to z a o risk at r g 90 yean
Gmstant relative risk (UNSCEAR 1988)

24
1.9
1.6

Lrukacmin
Liwarqua&aric doze-rapmse modd
Comtanl relative risk (USSCEAR 1988)

0.14" Doae is weighted dose nith neutrm RBE = 10. Valuu are propnimr besed on data for 1950-1987 [RU]. Age distribution d p q u l a t i m is that of Japan in'*1985 [JS].
Based m a linear dosc-response modcl nilh sex- and age-rt-expourre-specificrisks. Projection methods are described in foolndcs c and d of Table 30.
Risks computed using agc~pccificrisk d c i e n u and multiplicative risk projection (U21.
Projection was made using the excess atsdutc rirk modcl fit to the life span study pwlcd lcukacmia data using a non-linur dore-response model.

Table 32
Site-specific lifetime r i s k for solid tumours and leukaemia following II whole-body acute cxposure of 1 Sv a
Rirk of erpmwe-induced dcarh (REID) (%)
Sire of cancm

Mraemia
Oesophaw
StomachCalm

Femdes

Borh

1.3
0.3
0.9
0.5
22
0.4
1.8

L1
0.5
L4
0.6
1.2
0.3
1.0
0.3
3.1

Ovary
Oha

4.3

0.9
0.7
20
0.6
0.3
0.2
3.1
20
0.5
20

Tocal (except lakacmia)

10.4

11.4

10.9

11.7

12.3

i2.0

Li\u
Bladder
Lwg
Breast

Tctaf

"

Males

25

Projections are based a!nge-at-exposure-specificvalues umputed using dcath rates for Jap:~nin 1985 [JS]. Rntes were avcraged ovcr age a1 exposure using
the populatim d Japan in 1985.
Leukaemia risks were canpuled using the e x a s s absolute nsk modcl prcscntcd in IP331. This modd has a non-linear dose rcsponre and the risk varies withtime, MX and age at exposure. Projection b e y d the cuncnt follow-up was based m this model.
Solid t u m w risks were computed udng linear d a r e - r a p w e models uith age-at-exposure and scx-specific rdative risks and a 10-year latency period.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

127

Table 33
Standardized mortality ratios for all causes of death and for malignant neoplasms for nuclear energy workers
[Dl01
Y&dM
N u c h inrrnllarion
All c u e smortality ratios fa denrhs due lo

All

Cmer ofdW

digcaiu

-PI-

span

Conca of

Lmr
caw^

-L
-ir
sysrm

United Kingdom
United Kingdan Atomic Energy
Authority
Sellafield
Unitcd Kingdan Atanic Wcapms
ENblishmmt '

0.76
0.96

0.78
O.%

0.79 (108)1.07 (132)0.71 (153)
0.88 (147)

0.98 (38)0.93 (27)

1.2 (18)0.83 (10)

0.73

0.79

0.84 (90)0.64 (85)0.48 (11)0.44 (4)0.83 (107)0.45 (8)0.73 (25)

1.02 (14)0.51 (12)0.65 (30)0.67 (41)0.73(210)0.74 (33)0.m (490)
0.86 (310)1.38 (27)0.70 (50)0.94

0.75 (59)1.23(324)
1.36 (89)1.27 (850)0.84 (339)1.02 (21)0.83 (83)1.07

0.88 (4)0.89 (7)0.64 (9)0.74 (15)1.04 (28)0.83 (77)0.90 (19)0.98 (195)0.82 (103)0.93 (6)0.95 (32)
0.82

1.19 (2)1.34 (4)0.75 (4)0.88 (7)150 (16)
1.04 (40)0.S (4)
1.13 (92)0.71 (36)

United S h t n
United Nudear
PantenR&y Rats
Putsmouth
Oak Ridge National Labaatory
Oak Rid& Y-12
Oak Ridge, Y-12
Oak Ridge fedaal nudcar plan&
HanfadLindc Air Products
Savannah Rivu
N a d shipyards

0.83
0.n
0.63
0.78
0.73
1.00
0.89
1.11
0.78
L18
0.75
0.76

0.97
0.63
0.71
0.%
0.80
0.96
1.01
1.05
0.85
1.12
0.74
0.99

" Observed deaths in parentheses.
''

Substantial propdon of radiatim workers mmitorcd fa plutonium.
Substantial proportion of workers expcsed to tritium.
Workers employed 1943-1947.
Workers employed d y d a 1947.

LSO (18)
0.91

UNSCEAR 1994 REPORT

128

Table 34
Estimates of excess relative risk per sieverl for all cancers and lcukaemia f m n ~studies of workers In nuclear andrelated industries[a41

All cmccrs
Nucleminrlellarion

Ujeclr

Nwnba

4
&orh

L cukacmia

Excessrr[mM%r 90% CI

&k

Nwnba

ficcrs4

rcloriwrirk&ah

O l b ohcmorwnr

cmo

90% CIY 'Nu.ber4

R4&&(sv-')(5"-l)

CanadaAtomic Energy
OfCanada

8,97l

219

*

0.05

4.68-2.17

4 '

19.0

0.14-113

[G31

Ltd.
United Iiingdrm~
Alanic Energy
Authaity

21.545~tomicWeapons
Errablirhmcnt

9,369

Sellafield

10,157

Satid
Redstry for
Radiation

95.27

*

0.8

ns

7.6

720

-1.0-3.1

0.4-15.3-4.2-5.7-2.6

4

10

396

1,435

31

d

0.47

.0.12-1.2

47'

f

Uterus
Prostnte

8
42

F111

h g
Prostate '

85

PSI

Bladder
Multiple myeloma
1-yrnphohaematopiatic

14

7
27

M

[S14]

4.28

0.40-13.6

Thyroid

9

I=o]

-1.1

-0-1.9Ilodgkin's Qseare
Panncas

19

n

[GI61

wotlrets

United Statcr

Hadad

36.971

1,413

4.0

4-1.9

44

Oak Ridge

8,313

346

3.27

1.26-5.3

28

6.38 E-11.2-24

Lung

%

[wzll

35,933

1,036

-1.0

44.4

42 '

c0

c0-3.4Multiple mydoma

12

[GI91

National
Labaatory
Combined*' DCSCSare lagged by 10 years for cancers and 2 years f a I&cmia

f
6

Excluding larkaunia.
Excluding chrmic lyrnphocylic Icukacmia.
95% cmtidence interval.
Only among workers monitored for exposure to radionuclides.
Significant ecnd.
b a a r e nd la&.
Hador4 Oak Ridge Katiwal Laboratmy and Rccky Rats -tined.

u n l s othauise specified.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARClNOGENESIS

129

Table 35
Rlsk estimates for all cancer and leukaemia (excluding chronic lymphocyuc leukacmia) from occupational
studies and survivors of the atomic bombings in Japan

Excess rclorita rirk (SY-I)aYudV
All c a n e rm]United Kingdom
N a t i d Registry for Radiatim Workers

0.47 (4.12-LZO)

United Stated [ G l q
Hanford, Oak Ridge National L b o n t a y and Rocky Flats corntined-1.0 ( ~ 0 4 . 4 )United Kingdom .ldUeited S u t a mmbined [K21]0.23 (cW.63)*

S m i v a s of atomic banbinga in Japan
Males only, exposed over a p 20 years 1950-1970(liaear reladvc risk model, RBE = 10)0.33 (0.11-0.60)

Lculucrnia (ercludiog chronic lymphocytie Icukatmia)
United fingdom P<20]
National Registry for Radiatim Workers

4.3 (0.40-13.6)

United States [ G l q
Hanfmd. Oak Ridge National L b o r a t a y and R a k y Flats o ~ m t i n e d'

<O (4-3.4)

United Kingdom and United States combined [ U l ]1.7 (4-5.9)

Survivors of atomic h b i n g s in Japan Ill231
Males cnly e x p d over age ZO years 199-1970(linearquadratic rdativc risk modd, RBE = 10)

6.2 (27-13.8)

Estimates fm occupatimal rtudia bsvd on a linur rdativc risk modd. Doses lagged f a 10 ycus (all caaccr) a 2 years (Iwhemia). 90% a in prucnthcses.
Based on monitored w a k a s at sites qerated by British Nuclear Fuels (including SellaRcld), Ministry of Ddcncq United Kingdom Atomic Energy Authority
and Nuclear Ode.
Based m madtored uhite males employed at least six months at IIK
lianFord sit; Oak rid^ Natimal Laboratory or at the Rocky Flats nudear weapons p l m ~No low-dac-rate redudiw f a a a has been indudcd.
Likelihood maximized at a value that would have led to negative cxccrr rclativc r i b .

Table 36Comparison of risk estimates for mortality in survivors of atomic bombings in Japanand nuclear workers in the United Kingdom and in the United Slates

Collrcrirc~ e s rse h i r e rirk (sf1) 'L$&imc risks (%(dv)

AN cancer

Lcuknonin

All cancer

1.eukaemia

Averagedare'

cohortPmson.
ye=S

Sumvors of atomic bombings[s7]

75.9912185,000

10.500251

0.39(0320.46)

5.2(3.8-7.1)

4b
(3-5)

0.4
(0.3-0.55)

Nuclear workers in the
U a i t d f i n g d m [KZO]

95,217

1.211000

3.198

34

0.47
(-0.12-120)

4.3(0.40-13.6)

10(4-26)

0.76(0.07-2.4)

Nudear w a k e n in the
United States [ G l q

35.933705,000

ll40

32

4.99
(-6.38)<-15(-15-3)<D(~04.2)

4(~04.60)

Grovp

@

date
( m a St$

90% (7 in parentheses.
* Basedar ICRP [I101 with low4oe-rate reduction f.tctor of 2

UNSCEAR 1994 REPORT

130

Table 37
Cancer mortality among workers at the Mayak nuclear plant aIN41
Pcrcenrage of dcarhsfrorn cancer faroral gamma dare

Emprorecr orFacility A
Facility B
Bolh faalitia

4 . 0 sv

>1.0 Sv

5.7 r 0.6
4.3 t 0.4
1.8 2 0.4

9.4 t 1.2
8.1 2 0.6
8.4 t 0.5

Employees who started wak bcfae 1958.

Table 38
Cancer mortality amolig male workers at the hlayak actors and reprocessing plant
pu31
Reorfor * o r b s

Rep.0cctrih.g phi uwkas

1959-1953

1954- 1958

1949-1953

1954-1958

1.22
1286
45.947

4.92
509
15,730245
1,812
61.6497.16
L479
44,46419
26.3
0.72 (0.4-1.1)

197
153.2
1.2~(1.1-1.4)

55
61.3
0.9 (0.7-1.1)

2
1.41
1.42 (0.3-4.5)

25
7.11
3.52 (2.4-4.4)

6
3.59
1.67 (0.7-3.3)

Average cumulative p u m a dasc (Sv)
Kumba ot workas uich film t n d p recad
Pamu-ycars (to 31 t k m a b u 1989)

All caner
ObervedE V - da aedob~~cdle~p~

101
126.4
0.80 (0.74.9)
Leukncntia

0b.avtd

4
Obcwed/expatd '6168
LO6 (0.S-2.1)

Table 39
Lung cancer deaths in workers at the Mayak radiochemical plant
PI71
Cumulative cqui~~alurr
dare
in lungs (Sv)

Number of uvrkers

Obsavtd cares

Exprcrtd c a m

0.0.250.26-1.00
1.01-4.0

470
607
929

21

>4.00

340

0
4
19
22

All cases

2346

45

6.2
16.2

6.1
32.6

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARClNOGENESlS

131

Table 40
Mortality from breast cancer among female lun~inizingworkers in Ule United Kingdom

Ahsorbai dose /ram gamma rays
d . 2 Cy4 . 2 Gy

Women cM yean old at start ot work
0.51
678
27,29916
10.62
1.51 @ = 0.074) "(0.9.23)

0.085
255
8,569

Mean a h a b e d d m (Gy)
Kumba at risk
Person-years
Otserved
EVded
Obsaved/exp~ed
90% a

5
3.00
1.67 @ = 0.18) "(0.7-3.5)

Women x-30 yeen old a t s1at-I d w o r k
Mean a t s a b e d dcae (Gy)
Numba at nsk
Perm-years
Obscrr.cd

0.10
110
3.200
5
2.30
2 W (p = 0.09) "(0.84.4)

mead

Otscrr.cd/expdcd

90% Q

"

0.50
160
5.816
2
4.49
0.45 (p = 0.94) '(0.1-1.4)

Single-sided significance value.

Table 41
Odds ratios for morti~lityCrom leukaemia nniong residents of Utah exposed to radioactive rallout froni the
Nevada test site [S48]

Oddr rat&'Tcsr
fm ocndLow dasc(0.0-2.9 mGy)lntomediafc d m(3.0-5.9 mCy)

High dase(6.0-30 mCyJ

All leukaemias

1.00

1.W (0.91-1.27)

1.69 (1.01-2E4)

NSAll lcukacmia
except chronic lymphocytic lcukacnia

1.00

1.0s (0.89-1.30)

1.72 (0.94-3.12)

NS

Agc at exposue
0-19 years
2049 years
rM years

1.00
1.00
1.00

1.13 (0.74- 1.72)
0.99 (0.74-1.33)
1.17 (0.86-1.58)

3.97 (1.18-133)
1.39 (0.44.36)
1.36 (0.56-3.30)

SS

Agc at death
0-19 years
20-49 years
5044 years>65 years

1.00
1.00
1.00
1.00

1.20 (0.62-2.32)
0.92 (0.59-1.42)
0.82 (056-1.21)
1.26 (0.97-1.64)

5.82 (1.55-21.8)
297 (056-15.6)
1.48 (0.36-6.16)
1.06 (0.43-259)

p = 0.022
NS
NS
NS

Year of death
1952-1957
1958-1963
1964-19691970-1975
1976-1981

1.00
1.00
l.U
1.00
1.00

1.30 (0.43-3.88)
0.89 (0.60-1.33)
1.31 (0.89.1.91)
0.94 (0.63-1.40)
1.11 (0.78-1.57)

3.09 (0.76-125)
2.40 (0.81-7.08)
257 (0.76-8.67)
0.31 (0.03-2.74)
1.05 (0.25-4.41)

p = 0.041
SS

1.00
1.00
1.00

0.91 (058-1.43)
1.21 (0.94-1.55)
1.13 (0.91-1.41)
1.06 (0.76-1.50)
0.94 (0.65-1.37)
0.95 (0.38.2.36)

5.28 (1.66-16.7)
1.31 (050-3.42)
212 (1.034.35)
1.70 (0.614.73)
0.68 (0.18-Z.58)
3.66 (0.54-21.6)

p = 0.009

Cell type
Acute lymphmytic lwkacrniahe n m - I y r n p h y i c lcukacmia
Acute lcukacnias
Chroaic lymphocytic lcukaernia
Chronic no~-l-lymphocy~ic
lcukacmia
Ocher

*

1.00

1.00
1.00

NS

NS

NS
NS
NS

NS
p = 0.046

d d e o c e interval in parcnthcscs.
* 95%
I'rescna of acutc lymphocytic leuhernia and acute non-lymphocyt8c leukaemia plus three othcr ocutc Icuhemias not otheruisc specified.

SS

NS
NS

UNSCEAR 1994 REPORT132

Table 42
Risk estimates for site-specilic cancer mortality in the popul~ationliving along of the Techa River, 1950-1982[K181
Erhnic group

L&&

SomnchOaophugus

Lung

Exccu absolulc risk (10' I'YG~)" 'T a m s and Bashhrs
Russians
Tartars. Bashkirs and Rusians,
assuming m a r cffcd

0.93 (-0.097-1.96)
0.80 (-0.06-1.54)

I.& (-245-4.56)
260 (-1.57-7.17)

0.55 (-0.91-201)
4.35 (0.45-8.25)

1.51 (-1.36-4.38)-0.73 (-3.50-204)

0.85 (0.24-1.45)

1.84 (-0.96-4.64)

1.51 (-0.23-3.24)

0.61 (-1.34-256)

Excnr r r l r t i v c risk (Gy-') a
Tartars and Bashldrs
Russians
Tartars. Bashkirs and Rursiam.
assuming tanmar dfea

255 (-0.48-5.76)
4.97 (-1.83-11.8)

0.18 (-0.43-0.76)
0.86 (-0.55-227)

1.00 (-0.69-3.68)
231 (0.008-4.61)

0.53 (-0.48-1.54)
0.37 (-1.75-1.01)

3.24 (0.48-6.00)

0.33 (-0.25-0.91)

1.89 ( 0.09-3.70)

0.31 (-0.50-1.11)

aAoaunt taka d c h i c dilfncnces in backgrwnd rara. 9 0 2
in parrnlhcscs.
Since infarrnatica ar a u s c of deafh ir available for only two thlr& d deathq cxccar absdute risk is likely to be uodcrcstimattd.

Table 43
Incidence of leukaeniin in individuals surveyed in the Techa Klver and Kyshtym accident studies[K181

CN~Sof lcuknemin

Incidence role '( 1 6 PIT'

0.13

16.8
M.3
90.9
106.8
108.0

6
3
9
12
7

12.8 (5.6-253)
8.3 (23-21.3)
9.9 (5.2-17.3)
11.2 (6.5-18.2)
6.5 (3.0-12.2)

cmQd P U P 1Contrd goup 2

2956
4664

133
93

4.5 (3.9-5.2)
5.6 (4.6-6.6)

3
9

Dare in bone marrow
PY)

Person-years(1hourrmdFj

Techa Rhcr study
L13
0.82
0.59
0.29

Kyshlyrn arcidr~ltntudy

0.2-0.25
0.03-0.12 '0.003-0.03

ZL6
1129
357.9

23

l33 (3.6-343)
8 0 (4.4-9.1)
6.4 (4.4-9.1)

Control

526.7

28

5.3 (5.3-7.3)

ANNW A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

133

Table 44
Age-specific incidence of leukaernin, thymid cancer and all other cancers in the Ukrainian districts Polesskoe,
Narodichy and Ovruch, 1981-1990

Incidence rote ( I 8)a
Yem
0-14 yews

15-34 yews

45-6#years

6 yews

u (5)

4 (1)

5 (2)
10 (4)9 (4)
17 (7)
10 (4)
13 (5)4 (1)
18 (4)
9 (2)
10 (2)8 (2)
30 (7)
26 (6)
22 (5)
33 (7)

2(1)
5 (2)
2 (1)
5 (2)
3 (1)
2 (1)
5 (2)
7 (3)
0
3(1)

0
0
0
0
0
0
0
0
0
0

468 (199)
473 (199)
457 (189)
4 ~ (194)3508 (2m)
453 (195)
416 (177)
479 (201)479 (200)
OU (171)467 (106)565 (12.0
524 ( 116)
586 (346)
n 5 (154)577 (138)787 (186)
711 (166)81 1 (188)893 (190)

Ltvkvmia
1981
1982
1983
1984
1981,
1966
1987
1988
1989
1990

3 (1)
0
0
9 (3)
0
3 (1)
7 (2)
4 (1)
0
8 (2)

3 (2)
7 (4)
3 (2)
5 (3)
2 (1)
2 (1)
2 (1)
2 (1)
0
2 (1)

u (5)
3 (1)

u (5)

Thyroid cancer

1981
1982
1983
1984
1985
1986
1987
1988
1989
1990

0
0
0
0
0
0
0
0
0
1 1 (3)

2 (1)
3 (2)
0
2 (1)
0
0
2(1)
0
2 (1)
4 (2)
rUl other cancers

1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
of cavr in prathesa.
* Numba
Exduding larkacmir and thyrcid cancer.

0
3 (1)
0
9 (3)
6 (2)
10 (3)
10 (3)
7 (2)
4 (1)
0

44 (26)53 (31)52 (30)4s (2.7)
42 (23)J6 (23)63 (31)65 (32)45 (2?)
49 (22)UNSCFAR 1994 K13POIC1'

134

Table 45
Observed number of cnncers and standnrdized incidence r~tiosfor 1,762 women treated with "'I for
hyperthymidism at Mt~ssachusettsGeneral Hospital[G71
of IJ1f r e c c i w i from all r r c a r m t s COW

A-

4-239 M B q

None

Cancm sue210-369 M B q

a 370 M B q

O h t dSR"

O b s d

SR"

O h d

.YR "

O h r d9R'

AU malignant neoplasmsnAll digestive a g n s
Pancreas
BreastBrain
All a h a sites

8
2
10
1
13

1.0
1.1
29
1.0

41
13

0.9
1.1
1.7
1.4
1.8
0.4

53
15
3
14
0'
24

0.9
0.9
1.8
0.9
0
0.9

48
l3
3
18
3
14

LO
0.9
22
1
5
6.0
0.7

*

Nlrmbcr d w w c n
Abrrage a p at a t r y (years)
N u n b r d pnson-years

356
36.1
7.414.1

2
18

24

1

0.9

9
437
46.3
7,250.7

529
46.6
8,699.7416
535
6,146.0

SLR = S t a n d a d i d incidence ratio(oburved/cxpatal). Erpcded n m b a s w a e based on age- and alcndar-timc-rpcdficiocidencentes fa G M e c c i m ! ufite
wancn. Unless indicated standardid incidena ratios do not d f f a sipificantly horn 1.
Data not reported for any of thrsc sites indiddually.
Expected numtu is 0.7.
95% a:1.2-17.5.
' ExcludCd 14 wmcfl d C 6 c dose was M ~ ~ O \ M I .

ANNEX A: EPlDEMlOMGlCAL STUDIES OF RADIATION CARCiNOGENESIS

135

Table 46
Leukaernia incidence in patients in Sweden given l3'1 for treatment or diagnostic purposes
[HZ61

Gmup

TccP1

F d a
Mda

(mGy) "
(0.009)(0.058)
(35)
(39)
(221)

Dcre in h e m0.00aOl
0.u2al00.11-10
11-100>lo0
Age al upoaurc<40 ycan40-60 years
z60 years

T ~ m eafter urpontrc
2-9 ycus
10-19 years
a20 ycut

LuJoemia orha rhrur CLL

Chronic lympha~ularLocmia

All larkclemior

(CW,)

No.

SR

95% CINo.

SR

95% CINo.

SR

95% CI

130
104
26

1.09
1.13
0.94

0.91-1.29
0.92-1.37
0.62-1.38

65
43
22

1.08
1.08
1.09

0.84-138
a78-1.45
0.68-1.65

195
147

1-09
l.11
1-01

0.94-1.25
0.94-131
0.74-1.33

10
31
62
23
4

1.28
1.01
1.23
0.85
1.04

0.62-236
0.69-1.44
0.94-1.58
0.54-1.28
0.28-267

2
17
30
9
7

0.53
LlS
1.P
0.62
3.17

0.06-1.90
0.67-1.83
0.82-1.74
0.28-1.17
1.27-6.53

12
48

1.04
L06
L23
0.77

182

0.53-1.81
0.78-1.40
0.99-150
0.53-1.09
0.91-3.26

19
78
33

1.07
1.17
0.93

0.64-1.67
0.92-1.45
0.64-1.31

5

39
21

1.03
1.18
0.93

0.34-241
0.84-1.62
0.58-1.42

24
117
54

1.06
1.17
0.93

0.68-1.58
0.97-1.40
0.70-1.22

38
63
29

0.95
1.29
0.96

0.67-130
0.99-1.6s
0.64-137

0.71
1.22
1.26

0.38-1.21
0.83-1.7s
0.79-1.90

51
93
51

0.87
1.n
1.07

0.65-1.14~cn-iss
0.80-1.41

13
30
22

48

92

32
11

Table 47
Radiallon weighttng factors recomrnendrul by ICIU'[I101
T y p of mdinrion

E n a c range

R&b

wghia~
fmrar WRAll energies

1Ram

c10 keV, >20 keV
w2 MeV5
5

Neutrons

10-100 keV, 2-20 MeV

10Neutrons

0.1-2 MeV
All energies

20

F'l~amre, l c c t r q muoar
NanrauAlpha pprtida, fissicm fragments, heavy nudci

20

UNSCWR 1994 REPOK'I'

136

Table 48
Causes of death in patients in the German Thomtrast study [V9]Nwnbcrofdmrhr
Cause of death

Expard to n'Rormrr

Conadswith h i ~ hexcesses&urr
Liver e n n m
Liver cinhods
Myeloid leukacmia
Boae marrow failure

Disc-

I

396
168
35

40

29

4

2

3

thnt prnbahly have an excess

Caocer d h e extrahepatic tile durn
C a o m d the panacas

6
5

%

18
14
7
7
5
4

Nm-llodghb's lymphma

Plmacycoma
C a n m d the oesophagus
Cancer d the larynx
Bone sarurma.MalipanI rnesolhdiana

4

1
1
1

1

naurl

3

o

Peritmeal

20Lung a n m
Stanach canax
Brain a n o x
Prostate cancer
Cdoo c a n m
Rectal c a n m
Breast cancer
Kidncy canCMCU d the urinary bladderhy cancer
Chomc lymphatic leukaernia
Hodglun's disease
Adrcnnl mcm
Acute lymphatic lcukaemia

47
30
18
16
10
8
7
6
5
4
3
3

44
43
11
11
16
12
17
5
5
4
3
2

Dtcaser without appurrnt cxcrrn

2

1

1

0

T c d numba of derthr

2110

1,463

Total n m b a ol patients with follow-up

2,334

1.912

Table 49
Cancer Incidence in patients in the Danish Thomtrnst study [A121
Canccr site ar 9pc

O h r dSIR

95% CI

126
30
14
10
10
8.6
4.6
24
23
1.8
12
11

100-151
17-51
8.1-24
6.5-15
1.2-36
1.8-25
1.2-12
1.0-5.0
1.4-3.4
1.1-2.8
6.7-195.3-22

3.3

3.0-3.7

Cancer with nlntirtically significant e x c e s

Livn
Liver, n d primaryGall-bhddcr
Leukacmia
Nasal cadty
PeritoneumMultiplc mydomaw

Lung primary
Breast
MeCucUaOtha, wupedficd

79
14
15
?3

2
3
4

7
23
18
16
10
Cancer without rtatisticully significant excess

All ahn sites

93

AU sites (brain and CNS not included)297

ANNEX A: EPIDEMIOLOGlCALSTUDIES OF RADIATION CARCINOGENESIS

137

Table 50
Primary Liver cancers and leuknernia in patients in the Danish Thorotrast study[A121
Primary lirrr c ~ c w

OkLavtaanio

d number

SR

45
31
2
1

429
91
13
30

O

k

d numb5

SR

6
14
3
0

16
13

Age at injstioa

0-25years
26-45 years
46-59 years
2-59 years

Significance of trend

2
2h
31
20

Significance of trmd-

lime since injection
0-9 ycan
10-19 years
20-29 years
30-39 years>39 yean1

p = 0.011

p < 0.00001

Injcacd volume
1-9 ml10-19 ml
20-29 ml
>29 ml
~

4.8

n

o

o

84
I51
244

10
9
4

9.4
12
13

p = 031p < 0.0001
-

- -

-

-

-

-~
-

--

-

--

-

0
2
13

0
22

2

64

7

45
19

212
255

8

Sigaificance oC trmd

4

2

-

-

5.0
7.3
11
16
12

p = 0.07

p < 0.00001
lhtimated nicnn cuniulativc dose

Liv a0-2.9 Gy
3.0-3.9 Gy
4.0-4.9 Gy
5.0-5.9 Gy>S.9 Gy

Significance of acnd
Rcd boce m o w
0-0.9 Gy
1.0-1.9 Gy
20-2.9 Gy>9 Gy
Significance of trend

'

7
15

13
17
27

23
101
176
380

443

p < 0.00001

5
11
5

2

5.2
16

23
26
p = 0.0003

Mean dme to l i v a and red bone rnanw was ertirnald taking account d valume, lalacy period (lagged 10 years f a liver) and radiophysical propatiu,
induding d l - a h q i o a .

Table 51
Deaths from cancer and other causes In 592 workers In n thorlum processing plant a

P I
Came of dcathN&ofohrerrrd dcn~hr

Number of
apecrui &arb

Sandardized~tolityratio

95% CI

6.82
0.85
0.62
1.21
5.96
0.40
0.63
0.51
0.34
0.9 1
21.69

1.91

(1.01-3.25)

4.13
1.68

(1.34-9.63)(0.81-3.09)

1.75(1.26-2.39)

65.76
6.66
5.90

0.90
1.20
1.02

(0.69-1.17)(0.52.237)(037-222)

13

12.67
4.31

2.05
3.M

(1.33-3.01)(1.61-5.16)

5153

123.101.24(1.06-1.45)

Cancer

Digptlve o r p s

Rdum
Liver

Pameash g
ShaBrain. mual m a r syriem
Lymphosarccma
Hdgidn's disease
Lurlracmia

All cancas

13
1
2

5
10
1
3
1
2
2
38
O~hcrdireiucr

Circulalay system
Rapiratoay systcm
Digestive system5986All other csuws

Enanal causes
Muor vehicle a c d d c n ~ s
Unlrnown causes
All causer

26

Wnlrcrs were employed f a m e year a lmger in job catcgona wth hi* expaurea to thorium and thoron.
7 k a l paw-years 10,621; mean age at entry 33.4 r 13.1 SD: mean year at entry 1955.

ANNEX A: EPIDEMIOLOGICAL SWDIES OF RADIATION CARCINOGENESIS

139

Table 52
Variation with time since exposure in excess relutive risk of lung cancer per unit exposure to radon[n.XI1
C h k c fin k e r s a

Wcsr ~ohcmianwaniwn miners

98 1

503

1.0 C
0.5
0.4
0.2

1.0
0.5
0.2
0.0

0.05

4.001

Number of lung canws

X m e d a c e cxpcsure (years)

5-14
15-24
25-34
>35

p value f a hdaogeneity'

Background risk a d j d for agc and exposure t o arscnic.
Estimate d ERRIWLMadjusted for attained age and prcpauon of timc spent In the Jichymov mint Men who w a k e d in shafts with radon coamtrations
greater than 10 W L are excluded.
Value fixed at 1.0. O l h a values arc atimatcd ERRAVLM relative to this baseline category.
Parameta amstrained to be noaac@tivc in mcdd-fining

Table 53
Variation with athined age in excess relative risk of lung cancer per unit exposure Lo radon
In,XI]
C h b c tin miners a

Wen Bohuninn urnniwn miners

Age otrninal

h'vmbcr oflung cancers

Excess relariw rirk(% ~ 7 . h ~ ' )Age nrrninod

bms)

4 0

98
158
219
245
26 1

1.02
0.18
0.10
0.23
0.04

45
354
45-41

4.001

p value f a h d n o p n c i t y

50-54

55-59
60-64

A5
p n l w f a huaogrueity

omrsj

JS

Number oflung cancers
7

35
U1
310

h

s r d o n o riskRR
n~~(% WZM')

11.08
272
215
1.36

d.001

Background risk adjusted for age and arsenic exposure, but estimates oC WR/WLM include entire fdlow-up period and arc n u specific ro the 5-14 year periuld maximum effect. Values arc lower than in the West Bohemian &at because risk deocaxr with timc since exposure.
Estimale d ERRMrLU adjusted f a proportion d time spent in the Jhhymovmine and timc since cnposurc. Values quucd arc spodfic for men who had
spent I- than 20 p a ml d thar employment at the Jichymov mine and For exposures in the preceding 5-14ycan. ?hey are therefore higher than in the
Qlinac tin m i o a b a r .

UNSCEAR 1994 REPORT

140

Table 54
Lung cancer deaths and estimated excess relative risk in cohorts of miners a[I-211
Erpasad miners
Locarion

Nwnba
of minesmna
Grchorlwakia
ColaadoOntario
Nnvfcundland

apmue
WM)

Deathsfrom lung
CMC-

135,357
103,652
75,032319,701
35,02932,452
46,79768,05031,45425,54939.487

Zl7.4
198.7
807.2
30.8
367.3
80.6
110.3
17.2
2428
7.6
68.7

936
656
327
282
112
79

France13,6494,284
3.347
21,346
1,751
1,294
3,457
6,895
l,420
1,457
1,769

Total

60,570908,983

161.6

Sweden
New Mexim

Beaverlodp

Pon RadiumRadium Hill"

Personyews

Awagc

Uruxparad mtrers

NumberPmn-of miners

years

Denrhsfrom lungExcers reL71n.e risk perunit aposure
(5%

m.wl)

CMCQ

39
32
15

3,494
0
0
0
337
0
12
1.591
683
1,059
16

39,985
4,216
7,403
61,017
13,713841
12,15250,34522222
26,301
4,556

44
5
2
9
6
0
1
9
18
22
0

0.16 (0.1-0.2)
0.34 (0.2-0.6)
0.42 (034.7)
0.89 (0.5-15)
0.76 (0.4-1.3)
0.95 (0.14.1)
1.72 (0.66.7)
221 (0.9-5.6)
0.19 (0.1-0.6)
5.06 (1.0-12.2)
0.36 (0.0-1.3)

2,620

7,176

242,332116

0.49 (0.2-1.0)

M(

56

Entries include 5-year lag intend for cxposure to radm.
95% CI in pareutheses.
p c 0.001.

Table 55
Excess relative risk of lung cancer in relation to radon exposure rate for tin miners in China[Xll

Erpaure rare
(WLM a*')

c10
10-14
15-19
20-24
25-29
230
p value f a hctnogcncity

Nwnba ofFxess relarive risk per unit npasure(% WLM*)lung cancer rates

92

115
200
211
234
129

Unadjusrad for arsenic aparurc

Adjured fa arscnic a p a w e

1.74
1.15
1.09
0.83
0.70
0.48

0.49
0.37
0.37
0.23
0.19
0.16

~0.0010.003

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

141

Table 56
Relative risks of lung cancer and average expmum rates in cohorts of n ~ l n e nexposed to radon

Abwageupanve rare
(UZM ,-I)

Locarinn

Beavalodgc
Malmbergct 'France&tario

8
5
5
-10
10
-16

Gnuwall

New Mexico
ailla

aechmlonlda
Ncufcu~dlmd
POIIRadium
Colorado*

Excess relarive risk p a unit aparure y(% H Z M ~ a)Original

BUR N

21
3.6
0.58
L3
0.9

3.31
3.6 '

22?
28
-70

1.8
0.6
1.7
0.9

109

o.n

124

1.8

84

fH151
[RE]
[TI61
IM 141
P37I

0.2 7

[SBI
[XI1
[SVl

Pflsl

.f

0.9

[HI61
Pi181

ERFUW-H dcpmds on anained a p (see text).
Estimate given by original authors. Values may n u be companblc. as studies cova diffaca, ages and fdlowup pniodr' BEIR IV estimate, b a d on i n t d comparim but allowing the rdadvc risk p a WLM to vary betutccn cuhoru. for age 5544, 5-14 years aftn cxpoancI

When the rdative risk is assumed to be the same for all cohorts. ils estimated d u e is 25%p a WUI.
The average expowe rate for the &averlodge mine has b x n divided by 0.65, and the risk estimates multiplied by 0.65 to take into account thc r-t
rcvisim.
Estimates of exporutc rate may be tw low [ a ] .
Original papa d y dvcs estimates aftn allowing fm exposure rate &a,so they arc n a directly comparable.
Based m cumulative lagged expcsures of l e s t than 2,000 WLU mly.

dosimetry

Table 57
Variation in excess rclittlve risk of lung cancer mortality in men c x p o s ~ dLo c10 WI, in the West Rohen~ian
mining cohort a

P I
Expsurc rateguy

Frncriond change in risk from bardine category

Emplopcut at JPchymovdm (barcline category)
>2F&

1.00
1.80 (1.27-2.97)

T m since expcsurc (years)

5-14 (baseline category)
15-24
25-34
3 5

1.00
0.47 (0304.69)
0.24 (0.074.41)
0.00

Aciaincd a& (years)

>35
35-43
45-54
>50 (baseline category)

8.15 (2.70-21.1)
200 (1.04-3.76)
1.50 (1.04-236)
1.00

Excess rdativc risk per unit exposure for bascline category is 1.36%
95% CI in parentheses.
Tm-year window of cxporurc.
Parameta -strained
to be non-neptivc.

(95% CI: 0.52-353).

UNSCEAR 1994 REPORT

142

Table 58
Geographical sludles of non-occupationd exposure to radon and lung cancer
[S281
M e w
Colum~Iarea
ourcomc

Findings

Ref:

-we

CanadaLung cancer matality rates for
18 aties, 1966-1979

G e m u r i c mean WL bom survcy cf
14.000 homes done 1978-1980

No associatim d lung cancer mutality rates
with radm daughter levels[L9]

CllinaLung can= matality rates for twoareas oE the Guangdong Province,
1970-1983

By area: 'ccatrd' and "highbackground*

Similar lung cancer matality rates in the
two areas[HlO,

h a r k aod
SwedenYears d life lost f r a n lung cancer

Survcyr of residential radon exposures

Lung cancer rates in D a m a r k (lown radm)w a e significantly higha than in Swtdea(higher radon)

[G23]

Fdand

Comparison of lung c a m incidencewith national mean

Rcgimal suwey in seven municipalities Lung cancer rates did not dffu f r a nnational mean
in high radm arras

FranceLung canccr matality rates fm the two By area: from the geology, indoor
redons Limousin andradoa was @timaled to be 3-4 timcs
Poitou-(hareates, 1968-1982
higher in Limousin region

Italy

Lung o n c a matality rates for 3 1
towns in central Italy, 1969-1978

Japan

WI

Significantly lower lung cancer matality
rates in the high backgrouad regim

pill

Soil geologic features

Nm-significant increase f a males andfcmales in a r u s of higher exposure

PI

Lung cancer SMRs, 1952-1988,in
Misasa spa area and ndghbouring
umtrd area

Average outdoa radon concentrations

SMR f a lung cancer lower in higb radm
area than in control area, but diffamcc notstatistically significant[M451

NoraayLung canca inadcnce For
muniapalidcs

By muniapality: h s e d on measurcmenu in a b u t 20 h m e s in each

Significant mrrelatim between lung c a n a r
incidence and mean radon conccntratim[S29]

SusedenLung canca matality rates by county.
1969-1978

mimated bckgrcund gamma radiation. Significant correlatims f a lung cancer rates
assumed to correlate with radonin males and females with exposure[El]

United Kingdom

Lung cancer matality rates in England By munty: based on national survey of For males and femalg, lung c a n m rates
inversely associated with carnty a m a g c
ZOO0 homer
and Wales, by county, 1980-1983
radon levels

PI191

United Starts
FloridaLung canca in R a i d a compared a i t h
c d w u t a l cancer, 1981-1983

Residence in central Florida phospatemining r c i m

Twdold increase a m m g male non-smokas.
KO significant increase for male smdras a
U'anen[SlI

FloridaLung cancu in R a i d a compared with
cdor-ln n c a 1981-1963

Residence in threecounty area u i f hpotential raised indoor radon lcvcl

25 per cent increase in lung cancer

is311

FloridaDatabase on episodes d scrious illness
by ccunty

Stateuide survey of residential rndon
levelsLung cancer relatively Iw frequent in males PI31
with highest radon exposures and slightly
more frequent in such females, canpared lo
those with little eltposure

Iowa

Lung canca incidence For
muniapalities oT 1.000-10,000
residents, 1969-1979

Mean levcl d radiunl-226 in watersupplySignificantly increasing lung cancer
incidence for wales with expasurc; increase
not significant for females

jB31

Mainc

Lung cancer mortality rates by county,
1950-1969

Estimated county average Tor radon
cmcentratim in water

Significant associations in males andfemales hetween lung cancer mortality andexposurea151

Reading Prmg

Lung canca m a u l i t y rates by county.
1950-1969

By wunty: based on proportion within
Reading Prong

For the three counties moslly within theReading Prong area. lung cancer mutality
for men was significantly elevated in all
thrcc and for women, in two[r:6]

Reading P r m gLung canca matality rates by county,
1950-1979

By munty: based on geology; threelevels d cxposurc

For both sexes combined, lung cancer
mortality followed a gradient umsistent uithcxposurc

IAsl

Various ccuntics

Lung cancer mortality rates for 411
wunties. 1950-1%9

By cwnty: geometric mean
cmc,-ntration measured in >10 homes

For males and females, lung can=mortality rates i n v a s d y assodared withcounty-avcragc radm lcvcls[C13.

Lung canca mortality rates, 1950-1969 Presence of phosphate deposit, mine a Significant exccss of high rates d lungcancer in counties with phosphate mills
processing plant in county

F5]-

Various ccunties

C351

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARClNOGENESlS

143,
Table 59
Case-control and cohort studies of domestic exposure to radon and lung cancer
F281

Location

Sudy design

Subjects

Findings

Expacure m e a w e

Rc/.

Cmds
b r i oCorecontrol

27 cuv
49 contrds

Expaures recaomruded
mthcbasisof
mcasuremcnls

RR = 2 4 (95% CI: 0.8-7.1) uith rmdring
adjustment for exposed b ~ unexpaed.

[Lll

w i ~ J 3

Cpr-trol750 carer
750 owtrols

Year-loag alphs track
measurements

S o assodatim bclwca-~rdative risk andcumulative exposure[Llol

No assaiatim b e t w w radm and lung canca.
uith or uithoul adjustment f a a w d t e smoking
habits[B37

Chins
Shm~an.5

Gseaoad308 ~ w s
356 controls

Year-loag alpha t a c kmeasurements

SwedenStodmdm-trol

292 female rases
584 controls

Gmlogv 2nd li\ing nearground level

RR = 2 2 (95% CI: 1.2-4.0) f a cxpaed vr.
uncxposbd; expowrc<crpoow rdrtionahip not
found

1 ~ 1 ~ 1

Stockhdm

Gr~ontrol

210 female cases
209 controls

Year-long alpha track
measurements

Signiticant trend a f i a adjusting f a un&ing age
and municipality. RR = 1.0, 1.4, 1.7. 2.3 incategories d increasing cumulative n d m
exposure, but n d when adjusted la oaupancy

[PM,
S20]

Soh

Cnsccontrol

37 cases
178 controls

Residence type: w w 4'mixed' or staoc

RR = 1.8 (p c 0.05) for stone and mixed vs.
wood

[A31

South

Cascsontrol

177 cases
677 controls

Residence type andgeology, all homes;
mcasurcments lasting twomonths. some homes

Exposure associated with inmessed rick for nual.
but not urban. d w d l a s

[Ad]

Nolh

Carcaxltrol

15 non-smoka
15 smoker
e a v s o n t r d pain

Gmt~ction
characteristics

Estimated mean exposure siaificoncly higher f a
smddng cases than m o l s ; cxpesurc n adifferent f a wn-smolucs

PI]

Nu16

Car-trd589 male cases

Residence typc: wood anoa-wood

RR not increased, uith a without smoking
adjustment; RR i n c r d f a t h a e n e memployed in omrpatiau uaodated with lung[Dl1

S 8 2 d d a m ~ d s

453 living m u d s

caner

Wand

Cuclontrol

23 cares202 contrds

Residence type andmeasurements Isting farr
months uith alphasensitive film

RR = 4 3 (90% CI: 1.7-10.6) fa low- vs. highcxpcaurc h a n e type; RR = 2.7 (90% CI: 1.4-

Estimated mean cxporurca cornparable fa cam
and c m t r d s regardless of smoking

[PI]

F'l]

[EZ
a ]

185) for low- vs. high-e~cposurchome type bymeasurement; multipliatiw intmctim uithsmoking

Stockhdm

Case-control

11 nm-smoker
12 rmokcr
case-contrd pain

Coarvuaion
characteristics

Nationwide

Cssccontrol

1.360 cases
2847 controls

Three months alpha track

Compared uith <I40 Bq m-!

measurements

RR = 1.3 (95% CI: 1.1-1.6) f a 140-400 Bq rn-!
RR = 1.8 (95% CI: 1.1-29) for ,400 Bq m-l

United S b t e s
MarylandCohort298 cases o v a a
12-year period

Ilousing charaneristics

No associatims d' inadence rates
with housing charaauistics[SII]

New Jcrscy

Cohort752 persons who had
lived in houses with
documented highcrpcaure

Masurements uilhcarbon canister d c t r a o n

Excess lung w n c n in high exposure ban* but
not significant[Kll]

New Jersey

Casecontrol

433 cases
402 controls

Year-long alpha track
measurements

Significant trend in risk aft= adjusting f asmdring age and occupation; few highdosc
exposures[SSlI

UNSCEAR 1994 WI'OKT

144

Tahle 60
Cancer in two cohorts of young Seascale residents[GI,G2,G22]

DisurreCohorrCohortborn LO mothers r c d m r in Saaccalc

m o d imo S e ~ p c a l e41cr birth

O l u dFatal l a h e r n i a
M e t fatal cancer
Noo-fatal IcuLaemia
Nm-fad otho canm

5*
4

*

1'
2

0.53
1.07
0.08
1.11

06scn.ed

oprd

0
1'
0

0.54
1.50
0.03
201

3'

-

" F w with omd unda age 5 yean and one cue oCcfvmic m y d a d IarLcmia with onser at age 20 years.

* Nm-llcdgldn's lymphoma at age 3 years Wtlmr' hrmour at age 4 years. relropni~mcalsarcoma at age 6 ycan and maartltic quamarr cordnrmn oftcnguc'f

at a g 28 years.
h a at age 5 years.
Nm-Hodgha's l y m p h at age 1year and melanoma at age 28 years.
Melanoma at age 33 ycan.
Hcdgkin's l y m p b o u ~at age 26 years. nm-Hodghn's lymphana at age 9 years, and carcinoma d lung at age 21 y a m .

Table 61
Average annual equivalent dose (RBE = 20) to rcd hone marrow of a one-year-old childin Seascale fmm exposure to effluents of the Sellalield plant
is161

Yew

-

1955
1960
1965
1970
1975
1980
-

n e dtxI?.ttd avaagc amud bone marrow do^ horn natural n d i a d w is 990 $v

Equib8alenldose in Seascalcfim ScflqFld planI ''

Wv)
1200
120
58
120
330
170

-

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

145

Table 62
Factors associated wilh Increased risks of leukaemin In young people in West Cumbria[G211
Numba of C

~

U

Rdmie
risk

95% CI48

4.94

1.11-21.85

8

40

1.87

0.59-5.91

Matand aMomianl ndirtion in prepancy

4

31

1.74

a~6.82

Play on beach m a e &a comparcd rvith less o€ten than mmthly

13

15

0.89

0.37-217

Eating fish m a c &en compared with lea. oltcn than weekly

16

13

1.26

0.50-3.21

9
5

37
41
41
41

282
1.84
1.98
1.39

1.07-7.40
0.60-5.60
0.66-5.96
0.49-3.97

38

1.30
3.54
7.17

0.32-5.34
0.32-38.88
1.69-30.44

Furor

Paciri\.e

Neguiw

M a h a ' s age at individual's tirth 4 oanpsred with c25 yrr

4Fatha's age at individual's birth 240 mmparcd with c25 yrs

Fatha'r ocarpaticn
Sdlafidd
Irm and s t d industry
Farming
Chanical industry
Fatha's occuprtimd dose of radiatim b d a c ccaccpim
Rmious 6 months
1 4 mSv

5-9 mSv
P 10 DlSv

5
5

3
1
4

.*.......................................................................................... '......................... ...................... ................................ ............................ ...........................
*

Tolal
1-49mSv
9-99mSv
100 mSv
a

3
1

38

4

Thc lMal numba of cases ~ r i c dbctwccn questims because of variation in the source of the information.
Gmparad with ccatrdr not matched fa parish d residence.

1.12
0.69
6.24

0.314.05
0.08-5.73
L51-25.76

UNSCEAR 1994 REPORT

146

Table 63
Leukaernla and non-Hodgkin's lymphoma In young people living In Seascale: extent of paternal h d i a t i o n
before the child's conception[K27l
Nuntbcr of alfecred young people born

P & ~ M&
/ QM~
dare
(ms)

in Seascale

Elsdwe00.01-49.9
50.0-99.9

1
0
3

>loo

2"

3
1
0
1

Each of these categaiea indudcd an addttional individual who dewdoped leukamia willun :I few months of leaving Swscllc f a another addrcss; the ratha
d one had received a dose ol' m a e than 100 mSv and UTIS included in Gardncr'r 1990 series [G21].

Table 64
Leukaemia in young people living near three nuclear sites in southern England
P181
Rah of o b s d ro upccfed cases a a1 vwbw ogtr

Distance from sue(km)

0-4 yuus

5-14 years

0-14 yup-sJ

9 : 3.85

5-9
10-14

M : 10.56

1 : 3.83
11 : 10.33
21 : 14.11
3 : 7.06

10 : 7.68
31 : M.89
35 : 27.07
13 : 13.69

215a

14 : 12.96
10 : 6.63

Cases idudcd are from dislrids in which m a t than half of the population is within the dclincd area.

ANNEX A: EPiDEhllOLOGICAL STUDIES OF RADlAnON CARCINOGENESIS

1 (6)INCIDENCE

MORTALITY

Figure I.
Excess relative risk per sievert (CI: 90%) for incidence (1958-1987) and mortality (1950-1987)
from solid turnours, based on data of the life span study.

117

UNSCEAR 1994 REPORT

148

PART I: OESOPHAGUS
3.0 1

INCIDENCE

Life span study

Cervical cancer
cohortIifc span srudy

Cervical cancer
casecontrol

Lire span study

Ankylosing
spondylids

Massachusets~berculosis
fluoroscopy

PepticBenignLife span Mctropathia
study haemorrhagica gynaecological ulcer
diseaseAnkylodng
spondylitis

PART 111: COLON

3.0 1

INCIDENCE

Life span srudy

Cenical cancer
casecontrol

Life span Metroparhia
Benignstudy hacmorrhagica gymemlogical
DiscascFigum 11.
Comparative estimates of excess relative risk per sicvert (CI: 90%)
from cpidemlologlcal data on exposures under various conditions to low-LET radiation.

Pepticulcer

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

149

PART IV: LIVER

-

3.0

-

3.0 -

INCIDENCE

MORTALITY

h

-

5

25-

2.5

1

20-

2.0 -

$5 1.5 -

1.5

-

1.0

-

0.5

-

w

W

n:

1.0

-

I

il0 0.5 t5oo
4.5 -. . . . .

Life span study--g 2 5

3.01

Cervical cancer
cohort411.......

.

life span Ankylosing
study spondylitis-............. .-..........

Pepticulcer

Benign Metropathia
gynaecol. haemomhagica
diwasePART V: LUNGINCIDENCE

Life span study

Life spanstudy

Ankylosing M-chusetts
spondylitis tuberculosis
fluoroscopy

Pepticulcer

PART VI: BONE AND CONNECnVE TISSUEINCIDENCE

4b

Life s p a
study

Skin haemangiomain childhoodChildhoodradiotherapy

Figure 11 (mntinued)

Life spanstudy

Ankylosiog
spondylitis

150

UNSCEAR 1994 REPORTPART VII: SKlN (NON-MELANOMA)
3.0 1

INCIDENCE

Life span
study

Rochester~hyrnic
irradiation

N w Yorktinca capitis

Israelitinea capitis

Thyroid
irradiation

New York
post-parturnmastitis

Masachisem
tuberculosis
fluomscopy

Cervicalcanmcase-control

PART VIII: FEMALE B R E A S T
3.0-

INCIDENCEh7'

6 2.5-

%
a

2.0 -

g4

1.5 -

a

1.0

Lr]

-

iu 0.5 -

I

,b

+

i2

I

t

A

0

4.5

.............................

Life SpanStudy. . . . . . . . . . . . . . . . . . . . . . . -.

Ankylosing
Spondylitis

New York
Acute
Post-Partum
Mastitis.......................................

Lrchusetu?B
Fluomuopy

SwedishBreastIrradiation

INCIDENCE, cnn~inued

SmliosisSkinhaernangiorna

Rochester
thymicirradiation

Figure TI (mnlinued)... -................

Stanford
Hodgkin's
Disease

3.0 7-.-.-.....
Contnlaleral
Breastt-. ...
CenicalCancerCPse Control

MORTALITY

Life span
study

Canadatuberculosis
fl'J0-p~

151

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESISPART D(: BLADDERLife span study

Cervical cancer
case-control

Life span Merropathia
BenignAnkylosing
study
haernorrbagica gynaecological spondyliii
d i iPART X: BRAIN AND CENTRAL NERVOUS SYSTEMLife span
study.

Israeli,Skin
New York
lined caplt~s tinea capitis hacman iorna
in chiljhood

Figure I1 (continued)

Life spanstudy

Ankylosing
spondylitis

Pituitaryadenorna

UNSCEAR 1994 REPORT

152

PART XI: THYROID INCIDENCE
AGE-REUTED STUDIES

0

(1
4

1
0-9 yean

10-19 yean

>a0 yeanc20 years

Liie span study>20 years

Tuberculosis adenilis screening,
Life span
study

Israelitined capitis

Rochester
thymicirradiation

ChildhoodcancerSkin'omahaemanin chilgood

New capitis
York
tinea

SCREENING STUDIES IN CHILDREN
40

1

TomiVthymW
acne
screening

Lymphoidbyperplasia
screening

Thymusadeni5s
rnenlng

Michael Reeu.
tomi!,

scneung

Stanford
thyroid

Cervicalcancercasecontrol

Cervical cancer
cobon

ANNEX A: EPIDEMIOMGICAL STUDIES OF RADIATION CARCINOGENESIS

153

PART XII: L E U W M I A

7INCIDENCE

Lifespan
study

Tccha
CervicalRiver
cancerpopulation casecontrol

Breastcancertherapy

PART XIII:
3-0

1

ls-raeli Benign
trnea gynaecul.
capitis dl-

Cervical cancer
case-wnlrol

Pepdc
ulcer

EL

Ankylosing Benign
Mass. Metropathia
spondylitis gynaecol.
TB
haemordisease fluoroscopy rhagica

PART XIV: MULTIPLE MYELOMA

-

& 2J-

25

-

ia2 2.0 -

2.0 -

3.0

Metro- Ankylosing Mass.
spondylTB
itis
nuom-'PY

NON-HODGKIN'S LYMPtIOMA

3.0-

Pepticulcer

INCIDENCE

Life span study-

Childhoodcancertreatment

INCIDENCE

MORTALITY

h

14
W

1.5

-

1.5 -

1.0

-

1.0

-

-

0.5

OS

-

8

ii

b

a

4)

0

0

I

t

-0.5 - -Life span study

4b-0.5 -

Cervical cancer
caseoonlrol

rr

Mctropathia
baemorrhagica

F i g u r e I1 (continued)

Ankylosing
Benignspondylilis gynaecologicaldiseasePepticulcer-

UNSCEAR 1994 REPORT154- Age 10 years at time of bombings- - - - Age 25 years time of bombings......... Age 40 years at time oE b o r n b i n p
ai

5

10

20

30

TIME SINCE EXPOSURE (years)

5

10

20

30

TIME SINCE EXPOSURE (years)

Figure 111.
Temporal variation in excess absolute risk of leukaemia in the Life Span Study
for a weighted dose in bone marrow of 1 Sv.
V331

ANNEX A: EPIDEMIOLOGICAL STUDIES 01: RADIATION CARCINOGENESIS

155

"-F
Life Span Study-.-.

-..-..
..

3.0

a'

1.5 1.0-00

Slanford Hodgkin's
Disease Study d..

I
5

I

10

I
15

I
20

I
25

I
30

I
35

I
40

I
45

I
50

AGE AT EXPOSURE (years)

Figure IV.
Excess relative risk for the incidence of breast cancer in relation to age at exposure.

I

55

UNSCEAR 1994 REPORT

156

2 10
>

Y

y

0.8

CA

-

\ i1: \-MALES

a1 exposure 10 years

a

2

-

0.4

-

% 0.2 -

E
3.......... Age at exposure 50 years--

a 0.6 -c5

Age
Age ar exposure 30 years

z4 -.............................

W

0.4.......................................................... d

8 0.2 U0-------------------.

oh -

I
I
I
20
30
YEARS SINCE EXPOSURE

0

I
10

0

10

I

I

20

30

YEARS SINCE EXPOSURE

I

, 3

0-

-...................._.....

, , , , , , , , , , , ,

40

30

40
50
60
AlTAlNED AGE

70

80

40

30

40

70

80

50
60
AlTAINED AGE

FEMALESYEARS SINCE EXPOSURE

ATrAiNED AGE

YEARS SINCE EXPOSUREATTAINED AGE

Figure V,
Excess relative and absolute risk or mortality from solid tumours
for males (upper plots) and for femules (lower plots)
following an exposure of 1 Sv based on 1958.1987 mortalily data of the life span study.
v151

157

A N N M A: EI'IDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

-5 1

I

I

I

I

0

I

7
*

1

I

I

I

I

I
5

4

3

WElGlITED BONE MARROW DOSE (Sv)

1.50 10.25 10

CANCERS OTIiEK THAN 1-EUKAEMIA

I

I

I

I

I

1

2
3
WEIGHTED COIDN DOSE (Sv)

4

I

I

I

I

1
5

Figum VI.
Excess relative risk per Sv (and CI: 95%) for morhllty fmm leukaen~iaand cancers other than leukaemia

based on 1950-1987 dela of the life span study.
The lines connec~ingsmoothed points were obtained by weighting the estimated risk for the dose category (weight 0.5)
and the risks in ttle fwo adjacent categories (weight 0.25 eucll). f i r the highest dose category nqeights of 0.25 and 0.75
were used /or the nrrt to last and last category risk estinrates, respectively.

UNSCEAR 1994 REPORT158

WElGKIED INTESTINAL DOSE (Sv)

Figure VII.
Dose-response relationship for all ages and both sexes of solid tunlour incidence
based on 1958-1987 dah of Ule Llfe Span Study.
The excess relative risk per Sv is 0.63 (95% CI: 052-0.74).

[TI51

I

0.5

I
1

I

2

I
3

I
4

I
5

1

I

1 1 1 1

I

I

10

15

20 25

LOW-DOSE EXTRAPOLATION FACrOR
Figure VIII.
Dose-rate reduction hctors for cancer incidence derived from data on survivon: of the atomlc hornbinas.
-

The minimum wlues correspond to the maximum likelihood estimates of the lowdose atraplation factor (LDEF).
The points where the curves CIDSS the 95% likelihood level give the confidence bounds lor the LIlEE
Adjusted values account for bias introduced by random errors in individual dose &;mares.
w141

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

I

0

I

I

I

I

2

I

1
8

I

6

4

159

BREAsT DOSE (Gy)Figure IX.
Absolute risk of breast cancer incidence by single bmast in a study of women in New York
given radiotherapy for post-pnrtum masUUs, a a u s t e d for age at irrndiaUon and interval since irradiation.
Vertical bars are 90% CI and numbers in pnrentheses are number of cases.
~ 9 1

A

About 10 per dayCEx-smoker

E0

Never smoked

s1.0

DOSE (Sv)
Figure X.
Relative risk for incidence of lung cancer In the Life Spnn Study cohort associated with cigarette smoking
for T65 dose groups. Adjusted for city, sex, age a t exposum and a t t a l n d age.
Vertical bars indlcate 1 SE.

W I*

UNSCEAR 1994 REPORT

160

0.7 -

10 years

9

0.5 -- ---- ------.

7

I
I

0.6

\' \ \\I
I
I

30 years

*

\

I

0.3 -

I

50 years

0.2 -

I
I

T

I
I

-

0.1
0

0

\

' . ....... 0.4...\\,
'

'\

\

I
I
I
I

-

''
'

\

0.4 -

0.66

I

I

I

I

10

20

30

40

.

\

...;

1

0.23

\

I
1
50

\

\'.

C

\

60

I
1
70

I

I

80

90

AGE (years)
Figure XI.
13rsJectlon methods for lifetime risks of solid tumours in males.
The risk begins 5 years after exposure, is constant for 40 years and then either remalns constantor declines to intermediate level or zero at age 90.

Group A (Russian population)

0 Group B (Tartar and Bashkir population)

EFFECTIVE ROSE (Sv)

Figure XII.
Cancer mortality rates in populations living along the Techa River, USSR, 1950-1982.
LK181

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESISX M E AI;TER FIRST INTAKE (years)

Figure XIII.
Bone sarcoma appearance timer and average skeletal dosein persons in the Unitcd States exposed to 2 x ~ a .
w41

161

UNSCEAR 1994 REPORT

162

e a1 treatment

c26 years

0 26-45 years

CUMULATIVE ABSORBED DOSE IN THE LIVER (Gy)Males

0 Females

0

1

2

3

4

5

6

7

8

9 1 0 1 1 1 2 1 3 1 4

CUMULATIVE ABSORBED DOSE IN THE W E R (Gy)Figurc X?V.
Cumulative incidence of primary liver tumours among Danish patients exposed to Thorotrast.
[A 121

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

163

Figure XV.
Comparative estin~atesof excess relative risk per WLM (CI: 95%)
from epidemiologicrll studies of underground miners and from the combined data.
r211

CONCENTRATION (WL)
Figure XVI.
Estimated and fitted excess relative rbk of lung cancer per cumulative exposure
to radon and its decay products for the combined cohorts of miners.
T h e firred curves are from models with an erponential function (solid line) and a power function (dorred line).

11,211

164

UNSCEAR 1994 REPORTGlossary
Dosimetric terms and abbreviatioris
absorbed dasequantity of energy imparted by ionizing radiation to unit mass of matter, such as tissue.
Unit: gray (Gy). 1 Gy equals 1joule per kilogram.

DDREF

dose and dose-rate effectiveness factor. See also LDI:I:.

equivalent dosequantity obtained by multiplying the average absorbcd dose in a tissue or organ by aradiation weighting factor to allow for the different effectiveness of the various ionizing
radiations in causing harm to tissue. Unit: sievert (Sv). The fador for gamma rays,
x rays and beta particles is usually 1; for alpha particles and neutrons(100 keV-2 MeV)
it is 20.

effective dosequantity obtained by multiplying the equivalent dose in various specific tissues andorgans by a tissue weighting factor appropriate to each and summing the products. Unit:
sievert (Sv)low dose

expression used in :his document to refer to absorbcd doses in the range 0-0.2 Gy or
equivalent doses in the range 0-0.2 Sv. For further discussion see UNSCEAR 1993
Report. Annex F, "Influence of dose and dose rate on stochastic effeds of radiation".

low dose rate

expression used in this document to refer to dose rates of below 0.1 Gy per day for allradiations. For further discussion see UNSCEAR 1993 Report, Annex I.', "Influence ofdose and dose rate on stochastic effecls of radiation".

kerma

kinetic energy released per unit mass of material

LDEF

low-dose effcclivencss factor. The factor by which the slope of a pure linear model
fitted to the data should be divided to give the low-dose slopc, i.e. the linear term ina linear-quadratic dose-response model. Also dcsign;~tcdDDREF.

LET

linear energy transfer, indicating the amount of the iliili;il energy of a particle given up
per unit length of its path through material. as a result of ionizations and otherinteractions. IIigh-LET radiations include alpha particles and neutrons. Beta and gamma
radiations and x rays arc low-LET radiations.

radiation weighting factor

factor representing the different effectiveness of different radiations in inducing
stochastic effects

RBE

when low- and high-LET radiations cause an cqual level of effect, the ratio of theirabsorbed doses is called the RBE (relative biological effectiveness) of the high-LET
radiation relative to the low-LET radiation. For the purposes of routine radiation
protection, RBE is replaced by a single quantity (the radiation weighting fador) thatis judged to be reasonably representative of the range of RBEs for all relevant effects
at low doses and low dose rates; the product of absorbed dose in gray (Gy) andradiation weighting factor is termed the equivalent dose and is measured in sievert (SV).
Low-LET radiations are assigned a radiation weighting factor of unity, so an absorbed
dose of 1 Gy of low-LET radiation represents an equivalent dose of 1 Sv. An absorbed
dose of 1 Gy of alpha particles rcprescnt an equivalent dose of 20 SV.

slrielded kenna

kinetic energy released per unit mass of material after the incident radiation has passed
through intervening shielding matcrial

tissue weigluing factor

factor for a particular tissue rcprcsenting thc fraction;~l risk of the detriment (cancer
plus hereditary effects) attributed to that tissue when the whole body is irradiateduniformly

weighted doseused in this Annex to represent approsimate equivalent doses in the life span study ofthe survivors of thc atomic bombings, obtained by z~pplyinga value of RBE for
neutrons of 10.

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

165

Epidemiological terms and abbreviations
additive (absolure) risk modela model in which a unit of exposure induces an increase in the basic non-exposed
age-specific mortality rate. The increase is independent of and thus additive to theincreases caused by other exposures.

multiplicative (relative) risk modela model in which a unit of exposure induces an increase in the cancer mortality ratethat is proportional to the underlying age-specific rate.

ercess absolute risk (EAR)

the absolute difference between the instantaneous incidence or mortality rates between
two groups of people, e.g. those exposed to radiation at a given level and those
unexposeda c e s s relative risk (ERR)

relative risk minus one

person-years (PY)a unit of measurement combining persons and time, used as denominator in
instantaneous inadence and mortality rates. It is the sum of individual years that thepersons in the study population have been at risk of developing or dying from thecondition of interest.

relative risk (RR)

the ratio of the instantaneous incidence or mortality rates in two groups of people, e.g.
thosc exposed to radiation at a given level and those unexposed

standardized mortality ratio (SMR)

the ratio of the number of dcalhs obsenled in the study population to the number ofdeaths that would be expected i f i t had the same agc-. sex- and calendar-period-specitic
mortality rates as the standard population, which is often taken to be the relevant
national population. The SMR is sometimes expressed as a percentage (i.e. multipliedby 100).

standardized incidence ratio (SIR)

analogous to the SMR bur calculated for numbers of inadent cases of diseaseANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

167

References
Albert, R.E., R.E. Shore, N. Harley et al. Follow-up
studies of patients treated by x-ray epilation for tinea
capitis. p. 1-25 in: Radiation Carcinogenesis and DNA
Alterations. (F.J. Bums, A.C. Upton and G. Silini,eds.) Plenum Press, New York and London. 1986.
A2 Albo, V., D. Miller, S. Leiken et al. Nine brain
tumors (BT) as a late effect in children "cured" ofacute lymphoblastic leukaemia (ALL) from a single
protocol study. Proc. Am. Soc. Clin. Oncol. 4: 172(1985).
A3 Axelson, O., C. Edling and H. Kling. Lung cancer andresidency a case referent study on the possible
impact of exposure to radon and its daughters in
dwellings. Scand. J. Work Environ. Health 5: 10-15(1979).
A4 Armstrong, B.K., J.C. McNulty, L J . Levitt et al.
Mortality in gold and coal miners in Western
Australia with special reference to lung cancer. Br. J.
Ind. Mcd. 36: 199-205 (1979).
A5 Archer, V.E. Association of lung cancer mortality
with precambrian granite. Environ. Health 42: 87-91(1987).
A6 Axelson, O., K. Andersson, G. Desai et al. Indoor
radon exposure and active and passive smoking in
relation to the occurrence of lung cancer. Scand. J.
Work Environ. Health 14: 286-292 (1988).
A7 Axelson, 0. and L. Sundell. Mining, lung cancer andsmoking. Scand. J. Work Environ. Health 4: 46-52(1978).
A8 Ager, E.A., L.M. Schuman, H.M. Wallace el al. An
epidemiological study of childhood Icukaemia. J.
Chronic Dis. 18: 113-132 (1965).
A9 Aoyama, T. Radiation risk of Japanese and Chinese
low dose repeatedly irradiated population. J. Univ.
Occup. Environ. Health. 11(Suppl.): 432-442 (1989).
A l 0 Acquavella, J.F., L.D. Wiggs, R J . Waxweiler et al.
Mortality among workers at the Pantex weapons
facility. Health Phys. 48: 735-746 (1985).
A l l Archer, V.E., J.K. Wagoner and F.E. Lundin. Cancer
mortality among uranium mill workers. J. Occup. Med.
15: 11-14 (1973).
A12 Andersson, M. and H.11. Storm. Cancer incidence
among Danish thorotrast-exposed patients. J . Natl.
Cancer Inst. 84: 1318-1325 (1992).
A13 Akiba, S., J. Lubin, H. Ezaki et al. Thyroid cancer
incidence among atomic bomb survivors, 1958-79.
RERF TR/5-91 (1991).
A14 Abbatt, J.D. Human leukemic risk data derived fromthe Portuguese Thomtrast experience. p. 451-464 in:Radionudide Carcinogenesis. (C.L. Sanders et al.,eds.) CONF-720505 (1973).
A15 Andersson, M., B. Carstensen and J. Visfeld.
Leukemia and other related hematological disorders
among Danish patients exposed to Thorotrast. Radiat.
Res. 134: 224-233 (1993).
A16 Andersson, M., M. Vyberg, J. Visfeldt et al. Primaryliver tumors among Danish patients exposed toThorotrast. Kadiat. Res. 137: 262-273 (1994).
A17 Abelson, P.H. Mineral dusts and radon in uranium
mines. Science 254: 777 (1991).

A1-

A18 Alavanja, M.C.R., R.C. Brownson, J.H. Lubin et al.
Residential radon exposure and lung cancer among
non-smoking women. J. Natl. Cancer Inst. (1994, inpress).
B1 Baral, E.,L.E. Larsson and B. Mattsson. Breast cancer
lollowing irradiation of the breast. Cancer 40: 29052910 (1977).
B2 Baverstock, K.F. and D.G. Papworth. The UK radiumluminiser survey: significance of a lack of excess
leukaemia. Strahlentherapie 80 (Suppl.): 22-26 (1986).
B3 Bean, J.A., P. Isacson, R.M.A. Hahne et al. Drinking
water and cancer incidence in Iowa. 11. Radioactivity
in drinking water. Am. J. Epidemiol. 116: 924-932(1982).
B4 Beral, V., H. Inskip, P. Fraser et al. Mortality of
employees of the United Kingdom Atomic Energy
Authority 1946-1979. Br. Med. J. 291: 440-447(1985).
8 5 Beral, V., P. Fraser, L. Carpenter et al. Mortality of
employees of the Atomic Weapons Establishment. Br.
Med. J. 297: 757-770 (1988).
H6 Bithcll, J.F. and C.A. Stiller. A new calculation of the
carcinogenic risk of obstetric x-raying. Stat. Med. 7:
857-864 (1988).
B7 Black, D. Investigation of the possible increased
incidence of cancer in Western Cumbria. Her
Majesty's Stationary Office, London (1984).
B8 Boice, J.D. Carcinogenesis - a synopsis of humanexperience with external exposure in medicine. IIealthPhys. 55: 621-630 (1988).
B9 Brada, M., D. Ford, S. Ashley et al. Risk of second
brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br. Med. J. 304: 13431346 (1992).
B10 Brenner, DJ. and E.J. Hall. The interplay between
dose, dose protection and radiation quality. p. 167-177
in: Advanccs in Radiation Biology. Effects of Low
Dose and Low Dose Kate Irradiation. Volume 16.
(O.F. Nygaard, W.K. Sinclair and J.T.Lett, eds.)
Academic Press, San Diego, 1992.
B11 Boice, J.D.. N.E. Day. A. Andersen et al. Second
cancers following radiation treatment for cervicalcancer. An international collaboration among cancer
registries. J. Natl. Cancer Inst. 74: 955-975 (1985).
I312 Boice, J.D., M. Blettner, R.A. Kleinerman et al.
Radiation dose and leukaemia risk in patients treatedfor cancer of the cervix. J. Natl. Cancer Inst. 79:
1295-1311 (1987).
B13 Baverstock, K.F. and J.W. Stather (eds.). Low Dose
Radiation: Biological Bases of Risk Assessment.
Taylor & Francis. London, 1989.
B14 Bross, I.D. and N.S. Bross. Do atomic veterans haveexcess cancer? New results correding for the healthysoldier bias. Am. J. Epidemiol. 126: 1042-1050 (1987).
Rl5 Reral, V. and G. Reeves. Childhood thyroid cancer in
Belarus. Nature 359: 680-681 (1992).
B16 Boivin, J.F., G.B. Hutchison, F.B. Evans et al.
Leukaemia after radiotherapy for first primary cancers
of various anatomic sites. Am. J. Epidemiol. 123:993-1003 (1986).

168

UNSCEAR 1994 REPORT

B17 Blettner, M. and J.D. Boice Jr. Radiation dose andleukaemia risk: general relative risk techniques fordose-response models in a matched casecontrol study.
Slat. Med. 10: 1511-1526 (1991).
B18 Boice, J.D., E.B. I-lawey, M. Bletmer et al. Cancer inthe contralateral breast after radiotherapy for breast
cancer. N. Engl. J. Med. 326: 781-785 (1992).
B19 Boice, J.D. Jr. Radiation and non-Hodgkin's
lymphoma. Cancer Res. 52: 5489-5491 (1992).
B20 Boice, J.D., M. Blcttner. R.A. Kleinerman et al.
Radiation dose and breast cancer risk in patientstreated for cancer of the cervix. Int. J. Cancer. 44: 716 (1989).
8 2 1 Boice, J.D. Jr., G. Engholm, R.A. Kleinerman et al.
Radiation dose and second cancer risk in patientstreated for cancer of the cervix. Radiat. Res. 116: 3-55
(1988).
B22 Bithell, J.F. Epidemiological studies of children
irradiated in utero. p. 77-87 in: Low Dose Radiation:
Biological Bases of Risk Assessment. (K. Baverstockand J.W. Stather, eds.) Taylor & Francis, London,
1989.
B23 Bithell, J.F. and A.M. Stewart. Prenatal irradiation andchildhood malignancy: a review of British data fromthe Oxford survey. Br. J. Cancer. 31: 271-287 (1975).
B24 Brincker, H., H.S. Hansen and A.P. Andersen.
Induction of leukaemia by l3'l treatment of thyroid
carcinoma. Br. J. Cancer. 28: 232-237 (1973).
B25 Bowlt, C. and P. Tiplady. Radioiodine in human
thyroid glands and incidence of thyroid cancer in
Cumbria. Br. Med. J. 299: 301-302 (1989).
B26 Baverstock, K.F., D. Papworth and J. Vennart. Risksof radiation at low dose rates. Lancet 1: 430-433(1981).
B27 Baisogolov, G.D., U.G. Bolotnikova, I.A. Golstian etal. Malignant neoplasms of haematopoietic andlymphatic systems in workers of the first nuclear
facility (enterprise). I'robl. Onkol. 5: 553-558 (1992).
(in Russian)
B28 Bresiow, N.E. and N.E. Day. Statistical methods incancer research. The analysis o l case-control studies.
Volume I. IAKC Publication No. 32 (1980).
R29 Breslow, N.E. and N.E. Day. Statistical methods incancer research. The design and analysis of cohort
studies. Volume 11. IARC Publication No. 82 (1987).
B30 Buldakov. L.A. and A.K. Guskova. Effects of chronic
exposure to radiation. J. Physician 5: 34-39 (1991).
B31 Boice, J.D. Jr., D.L. Preston, F.G. Davis el al.
Frequent chest X-ray fluoroscopy and breast cancer
incidence among tuberculosis patients in
Massachusetts. Radiat. Res. 125: 214-222 (1990).
B32 Beck, W.L., D.L. Cookfair, C.L. Sowder et al.
Radiation dosimetry for epidemiologic lung cancer
study. p. 436-443 in: Epidemiology Applied to Health
Physics. CONF-830101 (1983).
B33 Berk, P.D., J.D. Goldberg, N. Murray et al. Increased
incidence of acute leukaemia in polycythemia Vera
associated with chlorambucil therapy. N. Engl. J.
Med. 304: 441-447 (1981).
8 3 4 Boice, J.D., C.E. Land and D.L. Preston. Ionizing
radiation. in: Cancer Epidemiology and Prevention.
(D. Schottenfeld and J.F. Fraumeni Jr., eds.) Oxford
Press, 1994.

B35 Baverstock, K.F. and D.G. Papworth. The UK radiumluminiser survey. p. 72-76 in: Risks from Radium andThorotrast. BIR Report 21. (D.M. Taylor et al., eds.)
British Institute of Radiology, London, 1989.
H36 Baverstock, K.F. and J. Vennart. A Note on radiumb d y content and breast cancer in U.K. radiumluminisers. llealth Phys. 44: 575-577 (1983).
1337 Blot, W.J., Z.Y. Xu, J.D. Boice et al. Indoor radonand lung cancer in China. J. Natl. Cancer Inst. 82:
1025-1030 (1990).
038 Boice, J.D., M.M. Morin, A.G. Glass et al. Diagnostic
X-ray procedures and risk of leukaemia, lymphoma,
and multiple myeloma. J. Am. Med. Assoc. 265:
1290-1294 (1991).
B39 Boice, J.D., J.S. Mandel, M.M. Doody et al. A healthsurvey of radiologic technologists. Cancer 69: 586-598(1992).
B40 Black. R.J., J.D. Urquhart, S.W. Kendrick et al.
Incidence of leukaemia and other cancers in birth andschools cohorts in the Dounreay area. Br. Med. J.
304: 1401-1405 (1992).
B41 Boice, J.11..M. Rosenstein and E.D. Trout. Estimationof breast doses and breast cancer risk associated withrepeated fluoroscopic chest examinations of womenwith tuberculosis. Radiat. Res. 73: 373-390 (1978).
B42 Baverstock, K., B. Egloff, A. Pinchera et al. Thyroid
cancer after Chemobyl. Nature 359: 21-22 (1992).
C1 Caldwell, G.G., D.B. Kelley and C.W. Heath.
Leukaemia among participants in military maneuvers
at a nuclear bomb test. A preliminary report. J. Am.
Med. Assoc. 244: 1575-1578 (1980).
C2 Caldwell, G.G., D.B. Kelley, M. Zack et al. Mortality
and cancer frequency among military nuclear test
(smoky) participants, 1957 through 1979. J. Am. Med.
Assoc. 250: 620-624 (1983).
C3 Checkoway, H., R.M. Mathew, C.M. Shy et al.
Radiation, work experience and cause specificmortality among workers at an energy researchlaboratory. Br. J. Ind. Med. 42: 525-533 (1985).
C4 Chmelevsky, D., A.M. Kellerer, H. Spiess et al. A
proportional hazards analysis of bone sarcoma rates inGerman radium-224 patients. p. 32-37 in: The Radiobiology of Radium and Thorotrast. ( ' . Gjssner et al.,eds.) Urban and Schwamenberg, Milnchen, 1986.
C5 Commission of the European Community. Thyroid
cancer in children living near Chernobyl. EUR 15248(1993).
C6 Committee on Biological Effects of Ionizing Radiation(BEIIt IV). llealth Risks of Radon and Other
Internally Deposited Alpha-Emitters. United States
National Academy of Sciences, National ResearchCouncil. National Academy Press, Washington, 1988.
C7 Cook-Mozaffari, P.J., S.C. Darby, R. Doll et al.
Geographical variation in mortality from leukaemia
and other cancers in England and Wales in relation lo
proximity to nuclear installations, 1969-1978. Br. J.
Cancer 59: 476-485 (1989).
C8 Curtis, R.E., R.N. IIoover, R.A. Kleinerman et al.
Second cancers lollowing cancer of the female genital
system in Connecticut, 1935-1982. Natl. Cancer Imt.
Monogr. 68: 113-137 (1985).
C9 Cuzick, J. and B. de Stavola. Mulliple myeloma: ause-control study. Br. J. Cancer. 57: 516-520 (1988).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESISC10 Curtis, R.E., J.D. Boice, R.A. Kleinerman el al. Summary: multiple primary cancers in Connecticut, 19351982. Natl. Cancer lnst. Monogr. 68: 219-242 (1985).
C11 Craft, A.W., L. Parker, S. Openshaw et al. Cancer inyoung people in the north of England, 1968-85.
Analysis by census wards. J. Epidemiol. Community
Health 47: 109-115 (1993).
C12 Committeeon Biological Effects of Ionizing Radiation(BEIR V). IIealth Effects of Exposure to Low Levelsof Ionizing Radiation. United States National
Academy of Sciences, National Research Council.
National Academy Press, Washington. 1990.
C13 Cohen, B.L. Experimental test of the linear nothreshold theory of radiation carcinogenesis. p. 319330 in: Environmental Radon: Occurrence, Control
and Health Hazards. (S.K. Majumdar et al.. eds.)
Pennsylvania Academy of Science, Pennsylvania,
1990.
C14 Curtis, R.E., B.F. Hankey. M.H. Myers et al. Risk ofleukaemia associated with the first course of cancer
treatment: an analysis of the surveillance,
epidemiology and end results program experience. J.
Natl. Cancer Inst. 72: 531-544 (1984).
C15 Court Brown, W.M., R. Doll and A. Bradford Hill.
Incidence of leukaemia after exposure to diagnostic
radiation in utero. Br. Med. J. 2: 1539-1545 (1960).
C16 Cragle. D.L., R.W. McLain, J.R. Qualters et al.
Mortality among workers at a nuclear fuels production
facility. Am. J. Ind. Med. 14: 379-401 (1988).
C17 Chmelevsky, D., H. Spiess, C.W. Mays et al. The
reverse protraction factor in the induction of bonesarcomas in radium-224 patients. Radial. Res. 124:
S69-S79 (1990).
C18 Cook-Mozaffari, P., S.C. Darby and R. Doll. Cancer
near potential sites of nuclear installations. Lancet 11:1145-1147 (1989).
C19 Cook-Mozaffari, P., F.L. Ashwood, T. Vincent et al.
Cancer incidence and mortality in the vicinity of
nuclear installations, England and Wales, 1950-1980.
Studies on medical population subjects. Her Majesty's
Stationary Office, London (1987).
C20 Cuzick, J. Radiation induced myelomatosis. N. Engl.
J. Med. 304: 204-219 (1981).
C21 Committee on Comparative Dosimetry of Radon in
Mines and Homes. United States National Academyof Sciences, National Research Council. National
Academy Press, Washington, 1991.
C22 Checkoway. H., N. Pearce, D.J. Crawford-Brown etal. Radiation doses and cause-specific mortality
among workers at a nuclear materials fabrication
plant. Am. J. Epidemiol. 127: 255-266 (1988).
C23 Castren, O., A. Voutilainen, K. Winqvist et al. Studies
of high indoor radon areas in Finland. Sci. Total
Environ. 45: 311-318 (1985).
C24 Curtis, R.E., J.D. Boice, M. Stovall et al. Risk ofleukemia after chemotherapy and radiation lreatment
for breast cancer. N. Engl. J. Med. 326: 1745-1751(1992).
C25 Carpenter. L.M. Studies of cancer among medical
personnel exposed /o radiation. Radiat. Res. 124: 351352 (1990).
C26 Clarke, E.A., J. McLaughlin and T.W. Anderson.
Childhood leukaemia around Canadian nuclear

169

facilities - Phase 11. Final Report. Atomic Energy
Control Board, Canada (1991).
C27 Court Brown, W.M., R. Doll, F.W. Spiers et al.
Geographical variation in leukaemia mortality inrelation to background radiation and other factors.
Br. Med. J. 1: 1753-1759 (1960).
C28 Conard, R.A. Late radiation effects in Marshallislanders exposed to fallout 28 years ago. p. 57-71 in:Radiation Carcinogenesis: Epidemiology andBiological Significance. (J.D. Boice Jr. and J.F.
Fraumeni Jr., eds.). Raven Press, New York, 1984.
C29 Cookfair, D.L.. W.L. Beck, C. Shy et al. Lung cancer
among workers at a uranium processing plant. p. 398406 in: Epidemiology Applied to Health Physics.
CONF-830101 (1983).
C30 Committee on Medical Aspects of Radiation in theEnvironment (COMARE). 3rd Report. (M. Bobrow,
Chairman). Her Majesty's Stationary Office, London(1989).
C31 Chen, S.Y., K.B. 1-Iayes, S.R. Liang et al. Mortality
experience of haematite mine workers in China. Br. J.
Ind. Med. 47: 175-181 (1990).
C32 Carpenter, L., P. Fraser, M. Booth et al. Smoking
habits and radiation exposure. J. Radiol. Prot. 9: 286287 (1989).
C33 Cardis, E. and J. Estkve. International collaborative
study of cancer risk among nuclear industry workers.
I. Report of the feasibility study; 11. Protocol. IARC
921001 (1992).
C . 4 Cardis, E., E. Gilbert, L. Carpenter et al. Combined
analyses of cancer mortality among nuclear industry
workers in three countries. lARC 941001 (1994).
C35 Cohen, B.L. Relationship between exposure to radonand various types of cancer. llealth Phys. 65: 529-531(1993).
C36 Curtis, R.E., J.D. Boice Jr., M. Stovall et al. The
relation of leukaemia risk to radiation dose aftercancer of the uterine corpus. J. Natl. Cancer Inst.
(1994, in press).
111 Damber, L.A. and L.G. Larsson. Lung cancer in males
and type of dwelling. An epidemiological pilot study.
Acta Oncol. 26: 211-215 (1987).
D2 Darby, S.C., J.1-I. Olsen, R. Doll et al. Trends inchildhood leukaemia in the Nordic countries inrelation to fallout from atmospheric nuclear weapons
testing. Br. Med. J. 304: 1005-1009 (1992).
D3 Darby, S.C., G.M. Kendall, T.P. Fell et al. Mortality
and cancer incidence in UK participants in UK
atmospheric nuclear weapon tests and experimental
programmes. NRPB-R214 (1988).
D4 Darby, S.C., G.M. Kendall, T.P. Fell et al. A
summary of mortality and incidence of cancer in men
from the United Kingdom who participated in the
United Kingdom's atmospheric nudear weapon tests
and experimental programmes. Br. Med. J. 296: 332338 (1988).
D5 Darby, S.C., E. Nakashima and H. Kato. A parallel
analysis of cancer mortality among atomic bomb
survivors and patients with ankylosing spondylitis
given X-ray therapy. J. Natl. Cancer Inst. 75: 1-21
(1985).
D6 Darby, S.C., R. Doll, S.K. Gill et al. Long-term
mortality after a single treatment course with X-rays

170

UNSCEARin patients treated for ankylosing spondylitis. Br. J.
Cancer 55: 179-190 (1987).
Darby, S.C. The contribution of natural ionizing
radiation to cancer mortality in the United States. p.
183-190 in: The Origins of Human Cancer. (J. Bruggc
et al., 4 s . ) Cold Spring IIarbor Laboratory Press,
New York, 1991.
Dionian, J., C.R. Muirhead, S.L. Wan et al. The risksof leukaemia and other cancers in Thurso fromradiation exposure. NRPB-R196 (1986).
Dobyns, B.M., G.E. Sheline, J.B. Workman et al.
Malignant and benign neoplasms of the thyroid inpatients treated for hyperthyroidism: a report of the
Cooperative Thyrotoxicosis Therapy Follow-up Study.
J. Clin. Endocrinol. Metab. 38: 976-998 (1974).
Doll, R. and S.C. Darby. Occupational epidemiology:
problems in reaching an overview. p. 105-112 in:
Health Effects of Low Dose Ionizing Radiation.
British Nuclear Energy Society. London, 1988.
Dousset, M. Lung cancer deaths in two French regionswith very different mean radon-222 concentration in
dwellings. SCPRI, France. 1990.
Draper, GJ., B.M. Sanders and J.E. Kingston. Second
primary neoplasms in patients with retinoblastoma. Br.
J. Cancer 53: 661-671 (1986).
Darnber. L. and L.G. Larssor~.Underground mining,smoking and lung cancer: a casecontrol study in theiron ore municipalities in northern Sweden. J. Natl.
Cancer Inst. 74: 1207-1213 (1985).
Davis, F.G., J.D. 13oice, 2. Hrubec et al. Cancer
mortality in a radiationexposed cohort of
Massachusetts tuberculosis patients. Cancer Res. 49:
6130-6136 (1989).
da Motta, L.C.. J. da Silva tlorta and M.H. Tavares.
Prospective epidemiological study of Thorotrast
exposed patients in Portugal. Environ. Rcs. 18: 162172 (1979).
Diamond. E.L., 11. Schmerler and A.M. Lilienfeld.
?he relationship of intra-uterine radiation tosubsequent mortality and development of leukaemia inchildren. A prospective study. Am. J. Epidemiol. 97:
283-313 (1973).
Dalheimer, A.R., A. Kaul, M.D. Said et al. Investigation on the effect of incorporated radioactive andnonradioactive particles and their synergism by longterm animal studies - physicochemical and biokinetic
properties of zirconium dioxide colloids.
Strahlentherapie 80 (Suppl.): 167-171 (1986).
DeGroot, L., M. Reilly, K. Pinnameneni et al. Retrospective and prospective study of radiation-induced
thyroid disease. Am. J. Med. 74: 852-862 (1983).
Doll, R. and R. Peto. The causes of cancer:
Quantilative estimates of avoidable risks of cancer in
the United States today. J. Natl. Cancer Inst. 66:
1191-1308 (1981).
Dobson, R.L., T. Straumc, A.V. Carrano et al.
Biological effectiveness of neutrons from Hiroshimabomb replica: results of a collaborative cytogenetic
study. Radial. Rcs. 128: 143-149 (1991).
Didson. RJ. Late rcsults of radium treatment of caranoma of the arvix. Clin. Radiol. 23: 528-535 (1972).
Dupree, E.A.. D.L. Cragle, R.W. McLain et al.
Mortality among workers at a uranium processing

facility, the Linde Air Products Company Ceramics
Plant, 1943-1949. Scand. J. Work Environ. Health 13:
100-107 (1987).
Darby, S.C., G. Reeves, T. Key et al. Mortality in acohort of women given X-ray therapy for metropathia
haemorrhagica. Int. J. Cancer 86: 793-801 (1994).
Darby, S.C., G.M. Kendall, T.P. Fell et al. Further
follow-up of mortality and incidence of cancer in manfrom the United Kingdom who participated in the
United Kingdom's atmospheric nuclear weapon tests
and experimental programmes. Br. Med. J. 307: 15301535 (1993).
Doll, R. Communication to UNSCEAR Seaelanat(1990).
Doshenko. V.N. Structure of death causes after
considerable occupational chronic total y-irradiation.
J. Mcd. Radiol. 8: 40 (1991).
Degteva, M.O.. V.P. Kozheurov and M.I. Vorobiova.
General approach to dose recons~ruction in the
population exposed as a result of the release ofrddioactivc wastes into the Techa river. S a . Total
Environ. 142: 49-61 (1994).
Doll, R., 1I.J. Evans and S.C. Darby. Paternal
exposure not to blame. Nature 367: 678-680 (1994).
Edling, C.. P. Comba, 0. Axelson et al. Effcds of
low-dose radiation - a correlation study. Scand. J.
Work Environ. IJealth 8 (Suppl. 1): 59-64 (1982).
Edling, C.. 11. Kling and 0. Axclson. Radon in homes- a possible cause of lung cancer. Scand. J. Work
Environ. I lealth 10: 25-34 (1984).
Edling, C., G. Wingrcn and 0. Axelson. Quantification of the lung cancer risk from radon daughter
exposure in dwcllinhs - :en epidemiological approach.
Environ. Int. 12: 55-60 (1986).
Eng, C., F.P. Li, D.11. Ahramson et al. Mortality fromsecond tumors among long-term survivors of retinoblastoma. J. Natl. Cancer Inst. 85: 1121-1128 (1993).
Enterline, P.E., G.M. Marsh, N.A. Esmen et al. Some
effects of cigarette smoke, arsenic and SOz on
mortality among US copper smelter workers. J.
Occup. Med. 29: 831-838 (1987).
Edmonds. CJ. and T. Smith. The long-term hazardsof the treatment of thyroid cancer with radioiodine.
Br. J. Radiol. 59: 45-51 (1986).
Ennow, K., M. Andersson, G. Engholm et al. Epidemiological assessment of the cancer risk among thestaff in radiotherapy departments in Denmark. p. 327333 in: Low Dose Radiation: Biological Bases of Risk
Assessment. (K.F. Baverstock and J.W. Stather, eds.)
Taylor & Francis, London, 1989.
Evans, R.D. The effcct of skeletally deposiled alpharay emitters in man. Br. J. Radiol. 39: 881895(1966).
Eatough, J.tl. and D.L. llenshaw. Radon and prostate
wncer. Lancet 335: 1292 (1990).
12abcr, M. Current (1981) status of the Danish
Thorotrast study. I lealth Phys. 44 (Suppl. 1): 259-260(1983).
Fabcr, M. Observations on the Danish Thorotrast
patients. Strahlentherapie 80 (Suppl.): 140-142 (1986).
Falk, H., N.C. Tclles, K.G. lshak et al. Epidemiology
of 'Ihorolrast-induced hepatic angiosarcoma in the
United Statcs. Environ. Iles. 18: 65-73 (1979).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

Folley, J.N., W. Rorges and T.Yamawaki. Incidenceof leukaemia in survivors of the atomic bomb in
Hiroshima and Nagasaki: Japan. Am. J. Med. 13: 311321 (1952) and ABCC TRI30-59 (1959).
Fleischer, R.L. A possible association between lungcancer and phosphate mining and processing. HealthPhys. 41: 175-178 (1981).
Fleischer, R.L. A possible association between lungcancer and a geological outcrop. Health Phys. 50:
823-827 (1986).
Flodin, U., L. Anderson, C.G. Anjou et al. A casereferent study on acute myeloid leukaemia,
background radiation and exposure to solvents andother agents. Scand. J. Work Environ. Health 7: 169178 (1981).
Flodin, U., M. Fredriksson, 0. Axelson et al. Background radiation, electrical work and some otherexposures associated with acute myeloid leukaemia ina case-referent study. Arch. Environ. Health 41: 77-84(1986).
Forastiere, F., S. Valesini, M. Arca ct al. Lung cancer
and natural radiation in an Italian province. Sci. Total
Environ. 45: 519-526 (1985).
Forman, D., P. Cook-Mozaffari, S.C. Darby et al.
Cancer near nuclear installations. Nature 329: 499-505(1987).
Fraser, P., L. Carpenter, N. Maconochie et al. Cancer
mortality and morbidity in employees of the United
Kingdom Atomic Energy Authority, 1946-86. Br. J.
Cancer 67: 615-624 (1993).
FGrst, CJ., M. Lundell and L.E. Holm. Cancer
incidence after radiotherapy for skin haemangioma: aretrospective cohort study in Sweden. J. Natl. Cancer
Inst. 80: 1387-1392 (1988).
Ford, D.D., J.C.S. Paterson and W.L. Treuting. Fetal
exposure to diagnostic X rays and Ieukaemia andother malignant diseases in childhood. J . Nail. Cancer
Inst. 22: 1093-1104 (1959).
Friedman, G.D. Phenylbutazone, musculoskeletal
disease and leukaemia. J. Chronic Dis. 35: 233-243(1982).
Fiirst, CJ., M. Lundell and L.E. Holm. Tumors afterradiotherapy for skin hemangioma in childhood. A
case-oontrol study. Acta Oncol. 29: 557-562 (1990).
Frome. E.L., D.L. Cragle and R.W. McLain. Poisson
regression analysis of the mortality among a cohort ofWorld War I1 nuclear industry workers. Radiat. Kes.
123: 138-152 (1990).
Flodin, U., M. Fredriksson and B. Persson. Multiple
myeloma and engine exhausts, fresh wood andaeosote: a case-referent study. Am. J. Ind. Med. 12:
519-529 (1987).
Flodin, U., M. Fredriksson, B. Persson et al. Acutemyeloid leukaemia and background radiation in an
expanded case-referent study. Arch. Environ. Health45: 364-366 (1990).
Frodkin, J.E., J.L. Mills, L.B. Schonbcrgcr et al. Kiskof leukaemia after treatment with pituitary growth
hormone. J. Am. Med. Assoc. 270: 2829-2832 (1993).
Fisenne, I.M., P. Perry, N.Y. Chu et al. Measured' 3 8 ~
and fallout 2 3 Q ~ uin human bone ash [.ram Nepal
and Australia: skeletal alpha dose. Health Phys. 44:
457-467 (1983).

171

Fiscnne, I.M., P.N. Dcmoleas and N.H. Harley.
Thorium excretion from a Thorotrast patient. The
Radiobiology of Radium and Thorotrast. Strahlentherapie (Suppl.) 80: 151-156 (1986).
Gardner, MJ., A.J. Hall, S. Downes et al. Follow-up
study of children born to mothers resident in Seascale,West Cumbria (birth cohort). Br. Med. J. 295: 822827 (1987).
Gardner, MJ., A J . tiall, S. Downes et al. Follow-up
study of children born elsewhere but attending schools
in Seascale, West Cumbria (schools cohort). Br. Med.
J. 295: 819-822 (1987).
Gribbin, M.A., J.L. Weeks and G.R. Howe. Cancer
mortality (1956-1985) among male employees ofAtomic Energy o l Canada Limited with respect tooccupational exposure to external low-linearenergytransfer ionizing radiation. Radiat. Res. 133: 375-380(1993).
Gilbert, E.S. Some effects of random dose
measurement errors on analyses of atomic bomb
survivor data. RERF TRl12-82 (1982) and Radiat.
Res. 98: 591-605 (1984).
Gilbert, E.S. and S. Marks. An analysis of themortality of workers in a nuclear facility. Radiat. Res.
79: 122-148 (1979).
Grcenc, M.II., E.L. ilarris, D.M. Gershenson et al.
Melphalan may be a more potent leukemogen thancyclophospharnide. Ann. Intern. Med. 105: 360-367(1986).
Goldman, M.R., F. Maloof, R.R. Monson et al. Radioactive iodine therapy and breast cancer. A follow-up
study of hyperthyroid women. Am. J. Epidemiol. 127:
969-980 (1988).
Greene, M.H., R.C. Young, J.M. Merrill et al.
Evidence of a treatment dose response in acute
nonlymphocytic leukaemias which occur after therapyof non-llodgkin's lymphoma. Cancer Res. 43: 18911898 (1983).
Gilbert, E.S. Mortality of workers at the Oak Ridge
National laboratory. llealth Phys. 62: 260-261 (1992).

GI1

G12

GI3

G14

Gilbert, E.S. and J.L. Ohara. An analysis of various
aspects of atomic bomb dose estimation at RERF
using data on acute radiation symptoms. Radiat. Res.
100: 124-138 (1984) and RERF TR19-83 (1983).
Griem, M.L., R.A. Kleinerman, J.D. Boice Jr. et al.
Cancer following radiotherapy for peptic ulcer. J.
Natl. Cancer Inst. 86: 842-849 (1994).
Goldman, K.P. Mortality of coal miners fromcarcinoma of the lung. Br. J. Ind. Med. 22: 72-77(1965).
Gray, R.G., J. Lafuma. S.E. Parish et al. Lung tumors
and radon inhalation in over 2000 rats: approximate
linearity across a wide range of doses and potentiation
by tobacco smoke. p. 592-607 in: Life-Span Radiation
Effects Studies in Animals: What Can They Tell Us?
(R.C. Thompson and J.A. Mahaffey, eds.) Office of
Scientific and Technical Information, United States
Department of Energy, 1986.
Graham, S., M.L. Levin, A.M. Lilienfeld et al. Preconception, intrauterine, and postnatal irradiation as
related to leukemia. Nall. Cancer Inst. Monogr. 19:
347-371 (1966).

1994 REPORT

Gum, F.W. and I1.R. Atkinson. Medical radiations andleukaernia: a retrospective survey. Br. Med. J. 1: 389-393(1964).
Gilbert, E.S., E. Omohundro. J.k B u h n a n et al.
Mortality of workcrs at the I-ianford site: 1945-1986.
Heallh Phys. 64: 577-590 (1993).
Gilbert, E.S., S A Fry. L.D. Wiggs et al. Analyses ofcombined mortality data on workers at the Hanford site,
Oak Ridge National Laboratory and Rocky Rats nudear
weapons plant. Radiat. Res. 120: 19-35 (1989).
Gibson, R., S. Graham, h Lilienfeld et al. Irradiation in
the epidemiology of leukemia among addts. J. Natl.
Cancer lnst 48: 301-31 1 (1972).
Gilbert, ES., D.L. Cragle and L.D. Wiggs. Updated
analysis of combined mortality data on workers at the
Hanford site Oak Ridge National Laboratory and Rocky
Flats Weapons Plant. Radiat. Res. 136: 408421 (1993).
Gilbert, E.S., G.R. Petcrsen and J.A. Buchanan. Mortalityof workers at the Hanford site: 1945-1981. Health Phys.
56: 11-25 (1989).
Gardner. MJ., M.P. Snee. AJ. l Iall et al. Results of casemntrol study of leukaemia and lymphoma among young
people near Sellaticld nuclear plant in West Cwnbria. Br.
Med. J. MO: 423429 (1990).
Gardner, MJ. Communication to the UNSCEAR
Seaetariat (1990).
Gj0rup. ILL. and l1J.M. Ilancen. lifetime loss throughlung cancer in Denmark and Swe&n in relation to rddon
levels. p. 165-169 in: tlealth Effect.. of l a w Dose
Ionising Radiation - Recent Advances and Their
Implications. 13ritish Nudear Energy Society, 1987.
Goss, S.G. Sizes of ppulation needed to detect anincrease in disease risk when the levels of risk in the
exposed and controls arc specified: examples fmm cancer
induced by ionizing ~idiation.Health Phys. 29: 715-721(1975).
Iianford. J.M., E. Quimby and V. F r a n ~ Cancer.
arising
many years after radiation therapy. J. Am. Med. k o c
181: 132-138 (1962).
H
e S.L.. MA. Tucker and R.T. Iloppe. Breast
cancer after mtment of HodgkinS disease. J. Natl.
Canax Imt 85: 25-31 (1993).
Harvey, E.B., J.D. Boice. M. Honeyrnan et ai. Prenatal
x-ray exposure and childhood cancer in twins. N. Engl.
J. Med 312: 91-545 (1985).
Heasman, M A . I.W. Kemp, J.D. Urquhart et al.
aildhood leukaemia in northern Scotland. Lancet 1: 266
and 385 (1986).
H e s , C.T., C V . Weiffenbach and S A Norton.
Environmental radon and cancer correlations in Maine.
Heallh Phys. 45: 339-348 (1983).
tlanmdt, S.L., R.S. Cox and R. McDougall. Thyroid
diseases aRcr treatment of llodgkin's disease. N. Engl. J.
Med. 325: 599605 (1991).
IIoffman, DA. Late elf& of 1-131 therapy in the
United Slates. p. 273-280 in: Radiation Carcino-genesis:
Epidemiology and Riologial Significance.(J.D. Boice Jr.
and J.F. 1:raumeni Jr.. eds.) Raven Press, New York,
1984.
Hoffman, D.A., W.M. McConahey, E.L. Diamond et al.
Mortality in women treatcd for hypmhymidism. Am. J.
Epidemiol. 115: 243-254 (1982).

H9

IIoffman, D.A., W.M. McComhey, J.F. Fraumeni Jr. et
al. Cancer ina&nce following treatment of hyperthyroidism. Int. J. Epidemiol. 11: 218-224 (1982).
HI0 Hofmann, W.. R. Katz and C. Zhang. Lung cancer
incidence in a Chincsc high background area - epidemiological results and theomtical interpretation. Sci. Total
Envimn. 45: 527-534 (1985).
1111 llolrn, L.E. Malignant disease following iodine-131
therapy in Sweden. p. 263-271 in: Radiation Carcinogenesis: Epidemiology and Biological Significance. (J.D.
Boia: Jr. and J.1:. Fnurncni Jr., eds.) Raven P~ess,New
York, 1984.
1-112 Ilolm, LE., K.E. Wiklund, G.E. Lundell et al. Thymid
caner after diagnostic doses of iodine-131: a
retrospe~ivecohort study. J. Natl. Canocr Inst 80: 11321138 (1988).
H13 Horta, J. da Silva, M.E. da Silva Horta, L. Cayolla daMotta et al. Malignancies in Portuguese thorotrast
patients. flealth Phys. 35: 137-151 (1978).
Hl4 Hill, C.K. A. llan and M.M. Elkind. Fission spectrum
neutrons at a low dose rate enhance neoplastictransformation in the linear dose region (0-10 ffiy). Int.
J. Radiat. Hiol. 46: 11-15 (1984).
HI5 Howe, G.K., R.C Nair, 1l.B. Newaxnbe et al. Lungcancer morblity (1950-80) in relation to radon daughter
exposure in a cohort of workers at the Eldomdo
Beaverlodge uranium mine. J. Natl. C a m r Inst. 77:357362 (1986).
1116 IIowe, G.R., R.C. Nair, t1.B. Newambe ct al. Lung
cincer mort7lity (1950-80) in relation to radon daughter
exposure in a cohort of workcrs at the Eldorado Port
ndium uranium mine: possible modification of risk by
exposure rate. J. Natl. Canccr Inst. 79: 1255-1260 (1987).
I117 Hohryakov, V.F. and S A Romanov. Lung canczr inradiochemical industry workers. Sci. Total Envimn. 142:
25-28 (1994).
1118 llornung, 1i.W. and '1'J. Meinhardt. Quantitative risk
assessment of lung cancer in U.S. uranium miners. HealthPhys. 52: 417-430 (1987).
H19 Haynes, R.M. The distribution of domestic radon
ancentrations and lung cancer mortality in England andWales. Radiat. Prot. Dosim. 25: 93-96 (1988).
H20 Hlofmann, W., R. Kak and C Zhang. Lung c a m risk at
low doses of a partidn. I lcalth Phys. 51: 457468 (1986).
H21 Hempelmann, I,.H., WJ. llall, M. Phillips et al.
Neoplasms in persons treated with x-rays in infancy:
fourth survey in 20 ycaa. J. Natl. Canox Inst. 55: 519530 (1975).
ti22 Hildreth, N.G., R.E. Show and P.M. DM-ky. The riskof breast cancer after irradiation of the thymls in infancy.
N. Engl. J. Mcd. 321: 1281-1284 (1989).
Hu Ilowe, G. Communication to UNSCEAR Seuetariat(1992).
1124 Iloffman, D.A.. J.E. lanstein. M.M. Morin d al. Breast
cancer in women with scoliosis exposed to multiple
diagnostic X rays. J. Niitl. Cancer Inst. 81: 1307-1312(1989).
1125 Hagtrom, I<.tI., S.R. Glasser, k13. Brill et al. Long term
effects of radioactive imn administered during humanpregnancy. Am. J. Epidcmiol. 90: 1-10 (1969).
Hi26 Ilall, P., J.D. Boice Jr., G. Berg et al. Leukaemia
incidence after iodine-131 exposure. Lancet 340 14(1992).

ANNEX A: EPIDEMIOLOGICAL STUD1IES OF RADIATION CARCINOGENESIS
H27 Holm, L.E. KE. Wiklund, G.E. Lundell et al. Cancer
risk in population examined with diagnostic doses of 13'l.
J. Natl. Cancer Inst. 81: 302-306 (1989).

H28 Hamilton, T.E., G. van Belle and J.P. LoGerfo. Thyroid
neoplasia in Marshall klandcrs exposed to nuclear fallout.
J. Am. Med. Assoc. 258: 629-636 (1987).
H29 I-Ioel, D.G. and G.E. Dinsc. IJsing mortality data toestimate radiation effeds on b m s t cancer inddence.
Environ. Health Perspea. 87: 123-129 (1990).
H30 Hakulinen, T., M. Kcnward, T. 1,uostarincn et al. Cancer
in Finland in 1954-2008. Incidence, Mortality and
PFeMlence by Region. Finnish Foundation for Cancer
R e , Helsinki, 1989.
H31 Hall. P., LE. Holm. G. Lundell et al. Cancer risk inthyroid cancer patients. Br. J. Cancer 61: 159-163 (1991).
H32 Hadjimichael, O.C., A M . Ostfeld, D.A D'Atri et al.
Mortality and cancer ind&nce experience of employees
in a nudear fuels fabrication plant. J. Occup. Med. 25:
48-61 (1983).
t B 3 I-latch, M.C., J. Beyca, J.W. Nieves et al. Cancer near the
Iluee Mile Island nudear plant: radiation emissions. Am.
J. Epidemiol. 132: 397-412 (1990).
H34 Hatch, M. and M. Susser. Background gamma radiationand childhood cancers within r n mills of a US nudear
plant. Int. J. Epldemiol. 19: 546-552 (1990).
H35 High Background Radiation Research Group. Healthsurvey in high background radiation areas in China.
Science 209: 877-880 (1980).
H36 Hempelmann, L.II., C.C. Lushbaugh and G.L. Voelz.
What happened to the survivors of the early I a s Alamos
nuclear aaidents? p. 17-32 in: The Medical Basis for
Radiation Acddent P r ~ p a r e d ~(KF.
s . Htibner and S.A.
Fry, eds.) Elsevier North ~Iolland,Inc.. 1980.
H37 Hodgon, J.T. and R.D. Jones. Mortality of a cohort oftin miners 1941-86. Br. J. Ind. Mcd. 47: 665-676 (1990).
kI38 Hcmhaw, D.L., J.P. Eatough and R.B. Richardson. Radonas a causative factor in induction of mycloid leukacmia
and other canccrs. lancet 335: 1008-1012 (1990).
H39 Hill, C and A Laplanche. Overall mortality and cancer
mortality around French nuclear sites. A letter. Nature
347: 755-757 (1990).
1140 Holm, L.E, P. Hall, ICE. Wiklund et al. Cancer risk after
iodine-131 therapy for hyperthyroidism. J. Natl. Cancer
Inst 83: 1072-1077 (1991).
H41 Holm. LE. Cancer risks after diagnostic doses of 13'1
with spedal reference to thyroid cancer. Cancer Detect.
Prev. 1x1): 27-30 (1991).
H42 Hatch, M.C. S. Wallenstein, J. Beyea et al. Cancer rates
after the Three Mile Island nuclear accident andproximity of residenoe to the plant. Am. J. I'ublic Health81: 719-724 (1991).
H43 Howe, G.R. Erects of dose, dose-rate and frddon onradiation-indud breast and lung cancers: the Canadianfluoroscopy study. p. 108-113 in: Proceedings of h e
International Conl'crcnce on Radiation Effcds andProtection, Mito. 1992. Japan Atomic Energy Research
I ~ t i t u t e Tokyo,,
1992.
H44 Howe, G.R., A.M. (7hiarelli and J.P. Lindsay.
Components and modifiers of thc healthy worker effect:
evidence from three occupational cohorts and implications
for industrial compensation. Am J. Epidcmiol. 1X
1364-1374 (1988).

173

Howe, G.R., J.L. Weeks, A M . Miller et al. A study ofthe health of the employees of Atomic Energy of Canada
Limited. IV. Analysis of mortality during the period
1950-1981. AECL-9442 (1987).
Harley, N.H., A B . Kolber, R.E. Shore et al. The skindose. and response for the head and neck in patients
irradiated with x-ray for tinea apitis: implications forenvironmental radioactivity. p. 125-142 in: Epidemiology
Applied to Health Physics. CONF-830101 (1983).
Harley. N.H. and E.S. Robbim. = ~ nalpha dose toorgans other than lung. Radiat. Prot. h i m . 45: 619-622(1992).
Hopton, P A , P A McKinncy, R.A Carhwight et al. Xrays in p r e p n c y and the risk of childhood cancer.
Lancet ii(8458): 773 only (1985).
Ishikawa. Y., T. Mori. Y. Kato et al. Lung caners
associated with ?horotrast exposure. High incidencc ofsmall cell carcinoma and implications for estimation ofradon risk Int. J. Cancer 52: 570-574 (1992).
Iwasaki, T., M. Minoua, S. Ilashirnoto et al. Noncanca
mortality and life expedancy in different MIUA
background radiation levels of Japan. p. 107-112in: Low
Dose Irradiation and Biological Defense Mwhanisnrr. (T.
Sugahara ef al., eds.) Usevier Science Publishers,
Amsterdam. 1992.
lnrernational Chernobyl Projed. A w s m e n t ofrddiological consequenm and evaluation of p t e d i v emeasures. Technical Report. IAEA, Vienna (1991).
International Commission on Radiation Units andMeasuremenls. The quality factor in radiation protection.
ICRU Report 40 (1986).
Ichimaru, M. and T.Ishimaru. Atomic bomb radiation
and adult T-cell leukemia. Acta Med. Nagasaki. %(I):170-175 (1991).
Interfittionttl Agency for Research on Cancer. IARC
Monographs on thc Evaluation of the Caranogenic Riskof Chemicals to Man: Some Miscellaneous
Pharmaceutical S u b t a n m . Volume 13. IARC Lyon,
1976.
Inskip, P.D., R.R. Monson, J.K. Wagona et al. Leukemia
following radiotherapy for uterine bleeding. Radiat. Res.
122: 107-119 (1990).
Inskip, P.D., R.R. Monson, J.K Wagoner et al. Cancer
mortality follouing radium treatment for uterine bleeding.
Radiat. Res. 123: 331-344 (1990).
International Agency for Research on Cancer. IARC
Monographs on the Evaluation of the Carcinogenic Riskof Chemicals to I lumans: Tobacco Smoking. Volume 38.
IARC, Lyon. 1985.
International Commission on Radiological Protection.
1990 Rccommcndatiom of the lnternational Commission
on Radiological larotedon. ICRP Publication 60.
Pergdmon Press, Oxford, 1990.
Iwasaki, T., M. Minowa. S. Ilashimoto et al. Cancer
mortality rates by geographic distribution and levels ofnatural radiation dose in Japan. p. 503-514 in:
Proaxding of the International Conference on HighLevels of Natural I<i~diation,Ramsr, Iran, 1990. bW-4
Vienna, 1993.
Inskip, P.D., R.A. Klcincrman. M. Stovall el al.
Leukemia, lymphoma and multiple myeloma following
pelvic rddiotherapy for benign disease. Radiat. Res. 135:
108-125 (1993).

174

UNSCEAR 1994 REPORT

Ichimaru. M. and K. Mabuchi. Multiple myeloma among
atomic bomb survivors. J. Radiat. Res. 32 (Suppl.): 168171 (1991).
Ichimaru, M., T. Ishimam, M. Mikami et al. Multiple
mydoma among atomic bomb survivors in IImshima andNagasaki. 1950-76: relationship to radiation dose absorbed by marrow. J. Natl. Canox Inst. 69: 323-328 (1982).
Inskip, PD., E.B. llarvey and J.D. B o i e Jr. lncidencc ofchildhood cancer in twins. Canox Causes Control 2: 315324 (1991).
Ishikawa, Y., T. Mori, Y. Kato et al. Systemic depositsof thorium in thorotmst patients with particular reference
to sites of minor storage. Radiat. Res. 135: 244-248(1993).
khikawa, Y., Y. Kato, T.Mori et al. Alpha-particle doseto the liver and spleen tissues of Japanese thoro-trast
patients. Health Phys. 6 3 0 : 497-506 (1993).
International Commission on Radiological Protection.
Protection Against Radon-222 at Home and at Work.
Annals of the ICRP q 2 ) . ICRP PuMication 65.
Pergamon Press, Oxford, 1993.
International Agency for Research on Cancer. IARC
Monographs on the Evaluation of Carcinogenic Risk to
Humans: Man-made Fibres and Radon. Volume 43.
IARC, Lyon, 1988.
Inskip, P.D..M. Stovall and J.T. Flannery. Lung cancer
risk and radiation dose among women treated for breast
cancer. J. Natl. Cancer Inst. 86: 983-988 (1994).
Jablon, S. Atomic bomb radiation dose estimation at
ABCC ABCC TRJ23-71 (1971).
Jablon, S. and [I. Kato. Childhood caner in elation toprenatal exposure to atomic-bomb radiation. Lancet I:
1000-1003 (1970).
Jacobson, A.P., P A Plato and N.A. Frigerio. The role ofnatural radiations in human leukemogenesis. Am. J.
Public Health 66: 31-37 (1976).
Jablon, S., 2. Hrubec, J.D. Boice Jr. et al. Cancer in
populations living near nudcar facilities. A survey ofmortality nationwide and incidence in two states. J. Am.
Med. PLssoc. 265: 1403-1408 (1991).
Japan, Ministry of Health and Welfare, Statistics andInformation Department, Minister's Secretariat. Vital
statistics 1985, Japan. Volume 1. Tokyo, 1985.
Jensen, O.M., D.M. Parkin, R. M a c l e ~ a net al. Cancer
registration, prinaples and methods. Int. Agency Res.
Cancer, Monogr. 95: 159-169 (1991).
Jablon, S. Do atomic veterans have e x a s cancer? New
mulls correcting for h e healthy soldier tias. Am. J.
Epidemiol. 126: 1214 (1987).
Kerber, K.A., J.E. Till, S.L. Simon et al. A oohort studyof thyroid disease in relation to fallout from nudear
weapons testing. J. Am. Med. A m . 270: 2076-2082(1993).
Kinlen, LJ., K Clarke and A. Balkwill. Patcrnal
prmnceptional radiation exposure in the nudear industry
and leukemia and non-l.Iodgkin's lymphoma in young
people in Scotland. Br. Med. J. 306: 1153-1158 (1993).
Kaul, A. and W. Nofb. Tissue dose in thorotrast patients.
Health Phys. 35: 113-121 (1978).
Kinlen, LJ. Evidence For an infedive cause of childhood
leukacmia: comparison of a Scottish New Town withn u c l e a r r e p m i n g sites in Britain. Iancrt 11: 1323-1327(1988).

K5
K6

K7

K8

K9

K10

Kl1

K12

K13

K14

K15

K16

K17

K18

K19

K20

K21

K22
K23

Kneale, G.W. and A.M. Stewart. Reanalysis of Hanford
data: 1944-1986 deaths. Am. I. Ind. Med. 23: 371-389(1993).
Knox, E.G., A.M. Stewart, G.W. Kneale et al. Prenatal
irradiation and childhood cancer. J. Soc. Radiol. Pmt 7:177-189 (1987).
Knox. E.G., AM. Stmart, E.A Gilman et al.
Background radiation and childhood cancers. J. Radiol.
Pmt. 8: 9-18 (1988).
Kopecky, KJ., E. Nakashima, T. Yamamoto et al. h gcancer, radiation and smoking among A-bomb survivors,
I Iiroshima and Nagasaki. RERF TR/l3-86 (1986).
Kate, H. and WJ. Schull. Studies of the mortality ofA-bomb survivors. 7. Mortality, 1950-1978: Part I.
Cancer mortality. Radial. Res. 90: 395432 (1982).
Kusiak, I<.& J. Springer, A.C. Ritchie et al. Carcinomaof the lung in Ontario gold miners: possible aetiologicalfactors. Br. J. Ind. Med. 48: 8084317 (1991).
Klolz, J.B., J.R. Petix and R.T. Zagraniski. Mortality of aresidential cohort exposed to radon from industrially contaminated soil. Am. J. Epidemiol. 129: 1179-1186 (1989).
Kellerer, A.M. and D. Barclay. Age dependenas in themodelling of radiation caranogenesis. Radiat. Prot
Dosim. 41: 273281 (1992).
Kaplan, I1.S. An evaluation of the somatic and genetic
ha~ards of the medical uses of radiation. Am. J.
ILoentgenoI. 80: 696-706 (1958).
Kinlen, LJ. The relevance of population mixing to theactiology of childhood leukaemia. p. 272-278 in: Medical
Response to Effeds of Ionising Radiation. (WA Cmsbie
and J.H. Gittus, eds.) Elsevier Applied Science, London
and New York, 1989.
Kaldor, J.M., N.E. Day, F. Petkisson et al. Leukemia
following chemotherapy for ovarian cancer. N. Engl. J.
Med. 3 2 1-6 (1990).
Kaldor, J.M., N.E. Day, E A Clarke et al. Lukemia
lollowing I lodgkin's disease. N. Engl. J. Med. 322: 7-13
(1990).
Kinlen, LJ., F. O'Brien, K. Clarke et al. Rural population
mixing and childhood leukaemia: effcctr of the North Sea
oil industry in Scotland, including hearea near Dounreay
nuclear site. Br. Med. J. 306: 743-748 (1993).
Kossenko, M.M. and M.O. Degteva. Canm mortality
and radiation risk evaluation for the T e h a river
population. .%. Total Environ. 142: 7389 (1994).
Kossenko, M.M., M.O. Degteva and N.A. Petrushova.
Estimate of the risk of leukaemia to residents exposed toradiation as a result of a nuclear accident in the southern
Urals. Phys. Soc. Resp. 2: 187-197 (1992).
Kendall. G.M., C.R. Muirhead. B.H. MacGibbon et al.
Mortality and occupational exposure to radiation: first
analysis of the National Registry for radiation workers.
Br. Med. J. U)4:220-225 (1992).
Kendall, G.M., C.R. Muirhead.B.H. MacGibbon et al.
First analysis of thc National Registry for radiation
workers. Occupational exposure to ionising radiation andmortality. NRPB-R251 (1992).
Kaxakov, V.S., E.1'. Demidchik and LN. Astakhova.
lhyroid cancer after Chemobyl. Nalure 359: 21 (1992).
Koshurnikova, N.A.. L.A. Buldakov. G.D.Bysogolov etal . Mortality from malignancies of the hemato-poietic andlymphatic tissues among personnel of the first nuclear
plant in the IJSSR. Sci. Total Environ. 142: 19-23 (1994).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESISK24 Kato, H., M. Mayumi, K Nishioka et al. The relationshipof HB surface antigen and antibody to atomic bombradiation in the Adult llcalh Study Sample. Am. J.
Epidemiol. 117: 610-620 (1983).
K25 Kondo, S. Health Effects of Low-Level Radiation.
Atomic Energy Research Institute, Kinki University.
Kink University P m , &!GI,
Japan and Medical
Physics Publishing, Madison, United States, 1994.
K26 Kozhcurov, V.P. and M. Dcgteva. Dietary intake
evaluation and dosimetric modelling for Ihe Techa riverresidents based on in vivo mezzurements of strontium-90
in teeth and skeleton. Sci. Tolal Environ. 142: 63-72(19%.
K27 Kinlen, U. Can paternal pmnoeptional radiationa m n t for the incrcasc of leukaemia and non-Hodgkin's
lymphoma at Seascale. Rr. Med. J. M6: 1718-1721(1993).
L1 Lees, R.E.M., R. S t d e and J.1.1. Robe-. A caseantrol
study of lung ~ n relativemto domestic radon exposure.
Int.J. Epidemiol. 16: 7-12 (1987).
L 2 Land, CE., J.D. Boice Jr., R.E. Shore et al. Bmst can=risk from low-dme exposures to ionizing radiation: resultsof parallel analysis of three exposed populations of
women. J. Natl. Cancer Inst. 65: 353-376 (1980).
I
3 Lubin, J.14.. Z. Liang, Z Hrubec et al. Radon exposure in
residences and lung cancer among women: combined
analyses of three studies. Canccr Cauxs Control 5: 114128 (1994).
LA Linos, A, J.E. Gray, A.L. Owis ct al. Low-dose radiation
and Icukaemia. N. Engl. J. Mcd. 30.2: 1101-1105 (1980).
L5 Lubin, J.11. Models for thc analysis of rddon-exposed
populations. Yale J. Riol. Mcd. 61: 195-214 (1988).
L6 Lewis, C.A., P.G. Smith, I.M. Stratron et al. Estimatedradiation doses to different organs among patients treated
for ankylosing spondylitis with a single course of X rays.
Br. J. Radiol. 61: 212-220 (1988).
L7 Land, C.E. Estimating cancer risks lrom low doses ofionizing radiation. Science 209: 1197-1203(1980).
I
S M e , N.P. Radon exposure and leukaemia. Lancet 11:
99-100 (1989).
L9 Utoumeau, E.G., Y. Mao, R.G. McGregor et al. Lungcancer mortality and indoor radon conocntrations in 18
Canadian cities. p. 470-483 in: Epidemiology Q l i c d to
Health Physics. CONF-830101 (1983).
L10 Moumeay E.G., D. Krewski, J. Qloi et al. Caseantrol
study of residential radon and lung cancer in Winnipeg,
Manitoba, Canada. Am. J. Epidemiol. 14014: 310-322(1994)L11 Land, C.E., N. Hayakawa, S. Machado et al. A casecontrol interview study of bmt canoer among JapaneseA-bomb survivors. I. Main effeds. Cancer Causes
Control 5: 157-165 (1994).
L12 Land. CE. and W.K. Sindair. 'the rclative contributionsof different organ sites to the total cancer mortality
associated with lowdosc radiation exposure. p. 31-57 in:with Ionising Ihdiation. Annals o l the
Risks &dated
ICRP 22(1). Pergamon I ' m , Oxford, 1991.
L13 Lloyd, K.D.. C.W. Mays, G.N. Taylor et al. Radium-224
retention. distribution, and dosimetry in bmgla. Radiat.
Rs. 92: 280-295 (1982).
L14 Lyman, G.H., C.G. Lyman and W. Johmon. Acsodationof leukemia with mdium groundwater contamination. J.
Am. M d . Assoc. 254: 621-626 (1985).

175

L'Abb6, K k , G.R. H o w , J.D. Bwch et al. Radon

exposure, cigarette smoking, and other mining experiencein the Beaverlod~uranium miners cohort. Health Phys.
60: 489-495 (1991).
Land, C.E. A nested casc-wntrol approach to interadions
between radiation dose and other fadors as c a w s ofcancer. RERF CRII-90 (1990).
Lubin, J.lI., Y. Qiao. P.R. Taylor et al. Quantitativeevaluation of the radon and lung cancer association in acase control study of Chinese tin mincrs. Canccr Res. 50:
174-180 (1990).
Litle, M.P., M.M. Hawkins, R.E. Shore et al. Timevariations in the risk of cancer following irradiation inchildhood. Radiat. Res. 126: 304-316 (1991).
land. C.E., N. Hayakawa. S. Machado et al. A casecontrol inteniew study of b w t ancer among JapaneseA-bomb survivors. 11. lnteradiom behKeen epidemiological fadors and radiation dme. Cancer Causes Con&
5: 167-176 (1994).
Land, C.E., M. Tokunap, S. Tokuoka cf al. Early ometof breast cancer among atomic bomb survivors: evidenceof a radiation-susceptible subgoup. l a n e t 342: 237(1993).
Lubin, J.H., J.D. Boice. C. Edling cf al. Radon and Lung
Cancer Risk. A Joint h l y s i s of Eleven Un&rground
Miner Studies. NIH Publication 94-3644. National
Institute of llcalth, Rcthesda. 1994.
Linet, M.S. and J.D. Boice. Radiation from (hernobyl
and risk of childhood leukaemia. Eur. J. Cancer 2 9 k 1-3(1993).
Land, C.E., Y. Shimosato, G. Saccornanno et al. A
comparison of the histology of lung cancers in uranium
miners and survivors of the atomic bombing ofHiroshima and Nagasaki. Radiat. Res. 134: 234-243(1993).
t i , F.P., J.F. Fnumeni Jr.. JJ. Mulvihill et al. A cancer
family syndrome in twenty-four kindreds. Cancer Res. 48:
5358-5362 ( 1988).
Machado, S.G., C.E. Land and F.W. McKay. Cancer
mortality and radioactiw fallout in southwestern Utah
Am. J. Epidemiol. 125: 44-61 (1987).
Mawn, I I.R., E.L. Saenger, S.R. %mas et al. Clinicallyimportant radiation-assodared thyroid disease. A
controlled study. J. Am. Mcd. Asoc 24J: 1802-1805(1980).
Mays, C.W. Cancer indudion in man from i n t dradioactivity. Health Phys. 25: 585-592 (1973).
Mays, C.W. Alpha-partide-induced cancer in humans.
Health Phys. 55: 637-652 (1988).
Mays, CW. and H. Spiess. Bone sarcomas in patients
given radium-224. p. 241-252 in: Radiation Carcinogenesis: Epidemiology and Biological Significance. (J.D.
Boioe Jr. and JE. Fnumeni Jr., eds.) Raven Press. New
York, 1984.
MacMahon, B. Leukemia clustcrs around nudear
facilities in Britain. Cancer Causes Control 3: 283-288(1992).
Mays, C.W., I-I. Spiess, D. Chmclevsky el al. Bonesarcoma cumulative tumor r a t s in patients injeded withradium-224. p. 27-31 in: The Radiobiology of Radium
and Thorotrag. (W. Gijdsncr et al.. eds.) Urban and
Schwanenberg, Miinchen, 1986.

176

UNSCEAR

M8

Manson, A, B. Ruden, R. Hall et al. Radiation-induced
breast cancer and long tern follow-up of radiotherapy for
benign breast disease. J. Natl. Cancer Inst. 85: 1679-1685(1993).
Monson, R.R. and B. MacMahon. Prenatal X-ray
exposure and cancer in children. p. 97-105 in: Radiation
Carcinogenesis: Epidemiology and BiologicalSignificance. (J.D. Boice Jr. and J.F. Fraumeni Jr., &.j
Raven Press, New York, 1984.

M9

MI0 Mori, T. and Y. Kato. Epidemiological, pathological anddosimetric status of Japanese Thorotrast patients. J.
Radiat. Res. 32 (Suppl. 2): 34-45 (1991).
MI1 Mori, T., Y. Kato, T. Kumatori et al. Epidemiologicalfollow-up study of Japanese Thorotrast cases, 1980.
Health Phys. 44 (Suppl. 1): 261-272 (1983).
M12 Mori, T., T. Kumatori, Y. Kato et al. Present status of
medical study on Thorotrast-administered patients inJapan. Strahlcnthcrapic (Suppl.) 80: 123-13(1986).
M13 Muirhead, C.R., B.K. Butland, B.M.R. Grccn et al.
Childhood leukaemia and natural radiation. Lancet 337:
503-501 (1991).
M14 Muller, J., W.C. Wheeler and J.F. Gentleman. Study ofMortality of Ontario Miners, 1955-1977.Part I. Report toOntario Ministry of Labour. Ontario Workers'
Compensation Board and Atomic Energy Control Boardof Canada (1983).
MI5 Mayya, Y.S., P.V. Joshi and K.S.V. Nambi. Radio-genic
cancer risk attributes for the Indian population based on
the revised ICRP risk coefficients. Radiat. Prot. Dosim.
46(2): 97-101 (19g3).
M16 Miller, B.G. and M. Jambsen. Dust exposure,pneumomniosis, and mortality of ma1 minen. Br. J. Ind.
Med. 42: 723-733 (1985).
M17 Muir, C., J. Waterhouse, 'l'. Mack et al. Cancer Incidence
in Five Continents. Volume V. IARC Publication NO.88.
LARC, Lyon, 1987.
M18 Morrison, H.I., R.M. Semenciw, Y. Mao et al. Cancer
tomortality among a p u p of fluorspar mines ex@radon progeny. Am. J. Epidemiol. 128: 1266-1275(1988).
M19 Miller, AB., G.R. Mowe, GJ. Sherman et al. Mortality
from breast cancer a ftcr irradiation during fluoroscopic
examinations in paticnls being treated for tuberculosis.
N. Engl. J. Mcd. 321: 1285-U89 (1989).
M20 Modan, B., A. Chetrit, E. Alfandary et al. Inneased riskof breast cancer after low-dose inadiation. Lancet 1: 629631 and 1012-1013 (1989).
M21 Mettler, F.A., M.K. Williamson, H.D. Royal el al.
Thyroid nodules in the population living around
Chernobyl. J. Am. Med. Assoc. 268: 616619 (1992).
M22 Muirhead, C.R. and G.W. Kneale. Prenatal irradiationand childhood cancer. J. Radiol. Prot. 9: 209-212 (1989).
M23 Mole, R.11. htenatal irradiation and childhood
cancer: causation or coincidence? Br. J. Cancer. 30:
199-208 (1974).
M24 Matanoski, G.M., P. Sartwell, E. Elliott el al. Cancer
risks in radiologists and radiation workers. p. 83-96
in: Radiation Carcinogenesis: Epidemiology andBiological Significance. (J.D. Boice Jr. and J.F.
Fraumeni Jr., eds.) Raven Press, New York, 1984.
M25 Miller, R.W. Effects of prenatal exposure to ionizing
radiation. Health Phys. 59: 57-61 (1990).

M26 Mole, R.H. Carcinogenesis following medical uses ofionizing radiation. p. 100-113 in: Low Dose
Radiation: Biological Bases of Risk Assessment. (K.F.
Baverstock and J.W. Stather, eds.) Taylor & Franas,
London. 1989.
M27 Mole, R.H. Alpha-particle irradiation and human
Icukacrnia. p. 153-158 in: Risks from Radium andThorotrast. BIR Report 21. (D.M. Taylor et al., eds.)
British Institute of Radiology, London, 1989.
M28 Mole, R.1-1. Carcinogenesis by thorotrast and othersources of irradiation, especially other a-emitters.
Environ. Res. 18: 192-215 (1979).
M29 Myers, M.11. and B.F. Hankey. Cancer survival in the
United States. p. 168-178 in: Cancer Epidemiology
and Prevention. (D. Schottenfeld and J.F. FraumeniJr., eds.) W.B. Saunders, Philadelphia, 1982.
M30 Mole, R.H. Fetal dosimetry by UNSCEAR and risk
coefficients for childhood cancer following diagnostic
radiology in pregnancy. J. Radiol. Rot. 10: 199-203 (1990).
M31 Mole, R.14. loniijng radiations and human leukemia. in:
Damcshek and Gum's hukaemia. 5th edition. (ES. Henderson and TA. Lister, &.) Saunders, Philadelphia, 1990.
M32 Mole, R.H. Childhood caner after prenatal exposure to
diagnostic x-ray examinations in Britain: a review. Br. J.
Cancer 62: 152-168 (1990).
M33 MacMahon, R. Some recent issues in lowexposureradiation epidemiology. Environ. Health Perspect. 81:
131-135 (1989).
M34 Modan, B. and A.M. Lilienfeld. Polycythemia Vera andleukemia - the role of ndiation treatment. Medicine 44:305-344 (1965).
M35 McLaughlin, J.R.. E.A. Clarke, D. Nishri et al. (hildhood
leukaemia in the vicinity of Canadian nuclear fadlitis.
Cancer Causes Control 4: 51-58 (1993).
t
M36 Mori, T., T. Kumatori, S. Hatakeyama et al. m(1986) s t ~ t uof the Japanese follow-up study of thethorotrast patients, and its relationships to the statisticalanalysis of the autopsy series. p. 119-124 in: Risks h m
Radium and Thorotrast. BIR Report 21. (D.M. Taylor eta]., eds.) British Institute of Radiology, London. 1989.
M37 Mayer, K., K.S. Pentlow, R.C. Marcove et al. Sulfur-35
therapy lor chondrosarmma and chordoma. p. 185-192
in: Therapy in Nuclear Medicine. (R.D. Spencer, ed.)Grune Stratton, New York, 1978.
M38 Marshall, J.H. and P.G. G m r . A theory of the indudionof bone cancer by alpha radiation. Radiat. Res. 71: 149192 (1977).
M39 Marshall, J.H., P.G. Gmer and R.A SchIenker. Dose toendosteal cells and relative distribution factors forradium-224 and plutonium-239 compared to radium-226.
IIealth Phys. 35: 91-101 (1978).
M40 Mole, R.H. Leukaemia induction in man by radionudides
and some relevant experimental and human obervations.
p. 1-13 in: The Radiobiology of Radium and Thomtrast(W. Giisncr et al., eds.) Urban & Schwarzenberg,
Munchen, 1986.
M41 Malanoski, G.M. Health effects of low-level radiation in
shipyard worken. Ileport of USDOE and St. Johns
I lopkins School of Hygiene and Public Health DE-ACO;?79EVlW5 (1991).
M42 Muirhead, C.R. Projcding radiation-induced cancer risks
across time and population. Soz. fidventi~med.M: 249254 (1991).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

M43 Muirhead, C.R., R. Cox. J.W. Stather et al. Estimates oflate radiation risks to the UK population. Documents of
the NRPB 4(4): 15-157 (1993).
M44 McLaughlin, J.R., T.W. Anderson. EA. Clarke et al.
Occupational exposure of fathers to ionizing radiation andthe risk of leukacmia in offspring - a case-control study.
Research Report, INFO-0424. Atomic Energy Control
Board, Canada (1992).
M45 Mifune, M., T. Sobue, 11. Arimoto et al. Cancer mortality
survey in a spa a m (Misasa, Japan) with a high radon
background. Jpn. J. Cancer Res. 83: 1-5 (1992).
M46 Michaelis, J., B. Kellcr, G. Ilaaf et al. Incidence ofchildhood malignancies in the vicinity of West German
nuclear power plants. C a m r Cam Control 3: 255-263(1992).
M47 McLaughlin, J.R., N. Krieger, M.P. Sloan et al. A
historical cohort study of cardiac catheterization duringchildhood and the risk of cancer. Int. J. Epidemiol. 22:
584-591 (1993).
M48 Mays, CW., D. Mays and RA. Guilmetk (cds.). Totalbody evaluation of a Thorotrast patient. Workshop heldin July 1990 at the National Cancer Institute, Bethesda.
Health Phys. 63: 1-100 (1992).
N1 Namti. K.S.V.. Y.S. Mayya and P.V. Jashi. Databaserequirements for deteding radiogenic cancer risks fromepidemiological sunteys in exposed populations. p. 10-13
in: Proceeding of S a n d National Symposium on
Environment, Jodhpur, India, 1993.
N2 Nambi, K.S.V., Y.S. Mayya. D.D. Rao et al. A study on
caner mortality in Tanpur-bard atomic energy
community. Arch. Environ. llcalth 47(2): 155-157(1992).
N3 Nambi, K.S.V., Y.S. Mayya and S.D. Soman. A cancer
mortality study in Bombay-based atomic energy
community: 1975-1987. Indian J. Cancer 28: 61-69(1991).
N4 Nikipelov. B.V., A.F. Lizlov and N.A Koshumikova.
Experience with the first Soviet nuclear installation(irradiation doses and personnel health). Priroda 2(February): 30-38 (1990).
N5 National Council on Radiation Protection andMcasurcments. Induction of thyroid cancer by ionizing
radiation. NCRP Report No. 80 (1985).
N6 Namti, KS.V., Y.S. Mayya and S.D. Soman An
analysis of cancer mortality among atomic energy
employees in Bombay and Tarapur. Curr. Sci. 59: 733736 (1990).
N7 National Council on Radiation Protedion andMeasurements. The relative biological effectiveness ofradiation d different quality. NCRP Report No. 10.i
(1990).
N8 Neuget, AI., E. Robinson. W.C. Lee et al. Lung cancer
after radiation therapy for breast cancer. Canccr 71: 30543057 (1993).
01 Bsterlind, A., J.11. Olsen, E. Lyngc ct al. Second cancer
following cutaneous melanoma and cancers of the brain,
thyroid, oonnective tissue, bone, and eye in Denmark,
1943-80. Natl. Canccr Inst. Monog. 68: 361-388 (1985).
0 2 O'Bricn, T.R.. 1'. Dccoufld and P.11. Ilhodes. Leukemia
and groundwater contamination. J. Am. Med. Assoc 257:
317 (1987).
0 3 Olsen, J.H., M. Andersson and J.D. Boice. Thorotrast
exposure and cancer risk. Ifealth Phys. 58: 222-223(1990).

177

Olsen, J.II., M. Andersson and J.D. Boim. Danish
epileptics given thorotrast. p. 116-118 in: Risks from
Radium and 'Ihorotrast. BIR Report 21. (D.M. Taylor etal., eds.) British Institute of Radiology, London, 1989.
0 5 Oppcnhcim, R.E., M.L. Griem and P. Meier. EtTcds of
lowdose prenatal irradiation in humans: analysis ofChicago lying-in data and comparison with other studies.
Radiat. Res. 57: 508-544 (1974).
P1 Pershagen, G., L. Darnber and R. Falk. Exposure to radonin dwellings and lung canoer: a pilot study. p. 73-78 in:
Indoor Air. Volume 2. Radon, Passive Smoking,Particulates and Housing Epidemiology. (B. Berglund etal., eds.) Swedish Coundl for Building Research,
Stockholm, 1984.
Pippard, E.C, kl. Mall, DJ.P. Barker et al. Cancer inF2'homozygoto and hcteruzygotes of ataxia-telangiec-tasia
and xeroderma pigmentosum in Britain. Cancer Res. 48:
2929-2932 (1988).
P3 Preston, D.L. and D.A. Pierce. ?he effect of changes in
dosimetry on cancer mortality risk estimales in the atomic
bomb survivors. RERF W - 8 7 (1987) and Radiat. Res.
114: 437-466 (1988).
P4 Preston, D.L.,H. Kato, KJ. Kopedry et al. Life Span
Study Report 10. Part I: (;mamortality among A-bomb
sunivors in Iliroshima and Nagasaki, 1950-82. RERF
W1-86 (1986) and Radiat. Res. 111: 151-178 (1987).
P5 Preston-Martin, S., A. Paganini-Ilill, B.E. IIenderson etal. Case-control study of intramnial meningiomas inwomen in Lns Angeles County, California. J. Natl.
Cancer Inst. 65: 67-73 (1980).
P6 Preston-Martin, S., M.C. Yu, B.E. llenderson et al. K i kfactors for meningion~asin men in Lns Angeles County.
J. Natl. Cancer Inst. 70: 863866 (1983).
P7 Pershagen, G., 0. Axelson, B. Clavcnsj6 et al. Radon in
dwellings and cancer. A country-widc epidemiologicalinvestigation. Institute of Environmental Medicine,
Karolinska Institute, Stockholm. IMM-rapport 2/93
(1993).
P8 Pottern, L.M., M. Kaplan, P. Larsen et al. Thyroid
nodularity after childhood irradiation lor lymphoid
hyperplasia: a comparison of questionnaire and clinicalfindings. J. a i n . Epidemiol. 43: 449-460 (1990).
P9 Pierce, D A , D.O. Stram and M. Vaeth. Allowing for
random errors in radiation expmure estimates for theatomic bomb survivor data. Radiat. Res. 123: 275-284(1990) and RERF W - 8 9 (1989).
P10 Parkin, D.M.. CS. Muir. S.L. Whelan et al. Cancer
Incidence in Five Continents. Volume VI. IARC
Publication No. 120. LARC, Lyon, 1992.
PI1 Pierce, D A and M. Vaeth. Canccr risk estimation fromthe A-bomb sunivor;: extrapolation to low doses, use of
relative risk models and other uncertainties. p. 54-69 in:
Low Dose Radiation: Biological Bases of Risk
kessmcnt. (K. Ravcrstock and J.W. Stather, &.)Taylor & 17rancis. London. 1989 and RERF CRn-89(1989).
P12 Prentice, R.L., Y. Yoshimoto and M.W. Mason. Ggarettesmoking and radiation exposure in rclation to cancer
mortality, Himshirrla and Nagasaki. REIW 11U1-82 (1982).
P13 Pierce, D.A. and M. Vacth. ' h e shape of the cancer
mortality dose-response curve for atomic bomb sunivors.
RERF W - 8 9 (1989) and Radiat. Ha. 126: 3 6 4 2(1991).

04

178

UNSCEAR 1994 REPORT

Preston-Martin, S., D.C. Thomas, S.C. White et al. Prior
exposure to medical and dental X-rays related to tumolsof the parotid gland. J. Natl. Cancer Inst. 80. 943-949(1988).
Preston, D.L., D A Pierce and M. Vaeth. Neutrons andradiation risk: a commentaly. RERF UpQte4 (1992-1993).
Polhemus, D.W. and R. Koch. Leukaemia and medical
radiation. Pediatrics 23: 453-461 (1959).
Preston-Martin, S., D.C. Thomas, Y. & B.E. Henderson.
Diagnostic radiography as a risk factor for chronic
myeloid and monocytic leukaemia (CML). Br. J. Cancer
59: 639644 (1989).
Polednak, A.P., A.F. Stehncy and R.E. Rowland
Mortality among women first employed before 1930 i n
the U.S. radium dial-painting industry. Am. J. Epidemiol.
107: 179-195 (1978).
Petersen, NJ., L.D. Samuels, H.F. Lucas et al. An
epidemiologic approach to low-level m ~ aexposure.
Public Health Rep. 81: 805-814 (1%6).
Pierce, D A and D.L. Presston. Joint analysis of sitespedfic caner risks lor the A-bomb survivors. Radiat.
Res. 134: 134-142 (1993).
Preston-Martin, S., W. Mack and B.E. Henderson. Risk
factors lor gliomas and meningiomas in males in Los
Anples county. Cancer Rcs. 49: 61374143 (1989).
Preston-Martin, S., M.C. Yu, B. Benton et al. N-Nitroso
compounds and childhood,brain tumors: a casecantml
study. Caner Res. 42: 5240-5345 (1982).
Pierce, D A , M. Vaeth and D.L. Praton. Variations withtime and age of the excess cancer risk among A-bomb
survivors. RERF T W l - 8 9 (1989) and Analysis of timeand age patterns in cancer risk of A-bomb survivors.
Radiat. Res. 126: 171-186 (1991).
Polednak, A.P. and E.L. Frome. Mortality among men
employed between 1943 and 1947 at a uraniumprocessing plant. J. Occup. Med. U. 169-178 (1981).
Petersen, G.R., E.S. Gilberk J.A. Buchanan et al. A casecohort study of lung cancer, ionizing radiation, andtobacco smoking among males at the Hanford site. HealthPhys. 58: 3-11 (1990).
Piao, C.O., S.A. Marino and T.K. Hei. Radiation, tobaar,
smoke condensate and oncogenic transformation. p. 185
in: 38th Annual Meeting of Radiation Research Sodety,
New Orleans, Abstract. Radiation Research Sodety,
Washington D.C.. 1990.
Pearce, N., I. Prior, D. Methven et al. Follow up of New
Zealand participants in British atmospheric nudear
weapons tests in the Pacific. Br. Med. J. 300: 1161-1166(1W.
Polednak, A.P., A.F. Stehney and H.F. Lucas. Mortality
among male workers at a thorium-processing plant.
Health Phys. .F4: 239-251 (1983).
Polednak, A.P. Bone cancer among female radium dial
workers. Latency periods and incidence rates by timeafter exposure: briclcommunication. J. Natl. Cancer Inst.
60:7 - 8 2 (1978).
Pershagen, G., Z.H. Iiang, Z. Hrubec et al. Residential
radon exposure and lung cancer in Swedish women.
Health Phys. 63: 179-186 (1992).
Pierce, D A , D.O. Strdm, M. Vaeth et al. The ermn-invariables problem: considerations provided by radiation
dose-response analyses of the A-bomb survivor data. J.
Am. Stat. ASOC.
87: 351-359 (1992).

Preston, D.L. Statistical issues in modelling radiation
effects on disease incidence. p. 141-146 in: The Future of
IIuman Radiation Research. BIR Report 22. (GB.
Gcrber, D.M. Taylor, E. Cardis et al., eds.) British
Institute o i Radiology, London, 1991.
Preston, DL., S. Kusumi, M. Tomonaga et al. C a n m
incidence in atomic bomb survivors. Part 111: Leukemia,
lymphoma, and multiple myeloma, 1950-87. RERF
TR/24-92 (1992) and Radiat Res. 137: S68S97 (1994).
Prisyazhiuk, A , O A Pjatak, V . k Buzanov et al. Cancer
in the Ukraine, post-Chemobyl. Lancet 338: 1334-1335(1991).
Preston, D.L., J.H. Lubin and D.A. Pierce "Epicmen:
Risk regression and data analysis software. H i m &International Corp., Seattle, Washington, 1992.
Penhagen, G., G. nkerbl~m, 0. Axelson et al.
Residential radon exposure and lung cancer in Sweden.
N. Engl. J. Med. 330: 159-164 (1994).
Parker, L., A.W. Craft, J. Smith et al. Geographicaldistribution of preconceptional radiation doses to fathers
employed at the Sellafield nuclear installation, West
Cumbria. Br. Med. J. 307: 966-971 (1993).
Parkin, D.M., E. Cardis, E. Masuyer et al. CXldhood
leukaemia following the (3hernobyl aocident: The
European Childhood Leukaemia-Lymphoma Incidence
Study (ECLIS). Eur. J. Cancer 29A: 87-95 (1993).
Rinsky, R.A., R.D. Zumwalde, RJ. Waxweiler et al.
Cancer mortality at a naval nudear shipyard. Lancet 1:
231-235 (1981).
Robinette, C.D., S. Jablon and D.L Preston. Mortality ofstudics in nuclear weapons tests participants. p. 1 4 7 in:Medi wl Follow-up Agency, National Research Counal.
National Academy Press, Washington, 1985.
Rossi, H.H. and A.M. Kellerer. The dose rate dependenceof oncogenic transformation by neutrons may be due tovariation in response during the cell cyde. Int. J. Radiat
Biol. 50: 353-361 (1986).
Ron, E. and B. Modan. Thyroid and other neoplasms
following childhood scalp irradiation. p. 139-151 in:Radiation Cardnogenesis: Epidemiology and BiologicalSignificance. (J.D. Boice Jr. and J.F. Fraumeni Jr., eds.)
Raven Prss, New York, 1984.
Ron. E., B. Modan and J.D. Boice Jr. Mortality a b
radiotherapy for ringworm of the scalp. Am. J.
Epidemiol. 127: 713-725 (1988).
Rowland, R.E., A.F. Stehney and H.F. Lucas. Doseresponse relationship for female radium dial workers.
Radiat. Res. 76: 368-383 (1978).
Rowland, ICE., AF. Stehney and 1I.F. Lucas. Doseresl'onse rela tionships for radium-i nduced bone sarcomas.
Health Phys. 44 (Suppl. 1): fi-31 (1983).
Radford, E.P. and K.G. St. ()lair Renard. Lung caner in
Swedish iron miners expafed to low doses of radon
daughlers. N. Engl. J. Med. 310: 1485-1494 (1984).
Roscoe. RJ.. K. Stwnland, W.E. Halperin et al. Lung
canox mortality among nonsmoking uranium miners
exposed to radon daughters. J. Am. Med. A m x 262:
629433 (1989).
Ron, E., B. Modan. J.D. Boice Jr. et al. Tumors of thebrain and nervous system after radiotherapy in childhood
N. Engl. J. Med. 319: 1033-1039 (1988).
lion, C., J. Lubin and A.B. Schneider. Thyroid cancer
incidence. Nature 360: 113 only (1992).

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

R12 Raliison, M.L.. B.M. Dobym, F.R. Keating et al. Thyroid
disease in children. A survey of subjects potentially
exposed to fallout radiation. Am. J. Med. 56: 457-463(1974).
R13 Rodvall, Y, Z M r u k , G. Pershagen et al. Childhood
cancer among Swedish twins. Cancer Cauxx Control 3:
527-532 (1992).
R14 Rimm. IJ., F.C Li, NJ. Tarbell et al. Brain tumors after
cranial irradiation for childhood acute lymphoblastic
leukemia. A 13-year experience from the Dam-Faber
Cancer Institute and the Children's Ilcspital. Cancer 59:
lSM-1503 (1987).
R15 Ron, E, B. Modan, D.L Preston et al. Thyroid neoplasia
following low-dose radiation in childhood. Radiat. Res.
lu): 516-531 (1989).
R16 Rodvall, Y., G. Pershagen, Z IIrubec et al. Prenatal x-ray
exposure and childhood cancer in Swedish twins. Int. J.
Can= 46: 362-365 (1990).
R17 Richarkon. R.B., J.P. Eatough and D.L. klenshaw. The
contribution of radon exposure to the radiation dase
received by red bone marrow. Int. J. Radiat. Biol. 57: 597(1989).
R18 Roman, E., V. Beral, L. Carpenter et al. Childhood
leukaemia in the Wot Berkshire and Easingstoke andNorth Hampshire Distrid Health Authorities in relation to
nuclear eslablishments in the vicinity. Br. Med. J. 294:
597602 (1987).
R19 Ron, E., B. Modan, D.L Preston ct al. Radiation-induced
skin caranomas of the head and neck. Radiat. Res. 125
318-325 (1991).
R20 Raabe, O.G., S A Book and NJ. Parks. Bone cancerfrom radium: canine dase mponse explains data for miceand humans. Science u)8: 61-64 (1980).
R21 Robbins, J. and W. Adams. Radiation effects in the
Marshall Islands. p. 11-24 in: Radiation and the Thyroid.
(S. Nagataki, ed.) Excepta Medica, Tokyo, 1989.
R22 Roes&, W.C. (ed.). Final report on the reassessment of
atomic bomb radiation dasimctry in IIiroshima andNagasaki. RERF (1987).
R23 Ron, E., D.L. Preston, K. Mabuchi et al. Cancer
incidence in atomic bomb survivors. Part IV: Comparisonof cancer incidence and mortality. Radiat. Re.. 137: S98S112 (1994).
R24 Roman, E., A. Watson, B. Beral et al. Casecontrol studyof leukaemia and non-Ifodgkin's lymphoma amongchildren aged 0-4 years living in West Berkshire andNorth Hampshire health districts. Br. Med. J. 306: 615621 (1993).
R25 Rooney, C., V. Beml. N. Mamnochie et al. Case control
study of prostatic cancer in employees of the United
Kingdom Atomic Energy Authority. Br. Med. J. 307:l391-1397 (1993).
R26 Rossi, H.H. and M. hider. Neutron RBE for A-bomb
survivors. RERF Update 3 (1 & 3-4) (1991).
R27 Ron, E. Communication to UNSCEAR SecrrL~riat(1994).
S1 Sindair, W.K. Science. Radiation Protection and the
NCRP. p. 1-56 in: 17th L.S. Taylor Lecture. NCRP,
Belhcsda, 1993.
S2 Saenger, E.L., G.E. 'Ihoma and E.A. Tompkins.
Incidence of leukaemia following treatment ofhyperthyroidism: Pmlirninary report of the Cooperative
Thyrotoximis Therapy Follow-up Study. J. Am. Med.
Assoc 205: 147-154 (1x8).

179

Sandler, D.P.. G.W. Comstock and G.M. Malanoski.
Neoplasms following childhood radium irradiation of themsopharynx. J. Natl. Cancer Inst. 68: 3-8 (1982).
Shore, R.E., R.E. Albert and R.S. Pastemack. Follow-up
study of patients treated by x-ray epilation for tinea
capitis. Arch. Environ. llealth 31: 21-28 (1976).
Sevc, J., E. Kunz. I-. TomSek et al. Cancer in man aftex
exposure to radon daughters. Ilealth Phys. 54: 2746
(1988).
Shimizu, Y., H. Kato, WJ. Schull et al. Life Span Study
Report 11. Part 1: Cornprison of risk d a e n t s forsite-spedfic cancer mortality based on the DS86 andT65DR shielded kerma and organ dases. RERF TR.ll2-87(1987); also ptblished asStudies of the mortality of A-bomb survivors.
9. Mortality, 1950-1985: Part 1. Comparison of risk
axfiaents for site-spedfic cancer mortality based on the
DS86 and T65DR shielded kerma and organ dmcs.
Radiat. Res. 118: 502-524 (1989).
Shimizu, Y., H. Kato and WJ. Schull. Life Span Study
Report 11. Pan 2: Cancer mortality in the years 1950-85
based on the recently revised dDSg (DS86). RERF TR/588 (1988); also publkhed asStudies of the mortality of A-bomb survivors.
9. Mortality, 1950-1985: Part 2: Canccr mortality basedon the recently revised doscs (DS86). Radiat Res. 121:
120-141 (1990).
Shore, R.E., R.E. Albert, M. Reed et al. Skin cancer
incidence among children irradiated for ringworm of thescalp. Radiat. Rcs. 100: 192-204 (1984).
Shore, II.E., N. llildrcth, E. Woodard et al. Breast cancer
among women given X-ray therapy for acute ptpartum
mastitis. J. Natl. Cancer Inst. n.689-696 (1986).
Shore, R.E., E. Woodard, N. Mildreth et al. Thyroid
tumors following thymuc irradiation. J. Nall. Cancer Imt.
7 4 1177-1184 (1985).
Simpson, S.G. and G.W. Cornstock. Lung c a m r andhousing characteristics. Arch. Environ. llealth 38: 248
251 (1983).
Smith, P.G. and R. Doll. Late effeds of x-irradiation inpatients treated for metropathia haemorrhagici. Br. J.
Radiol. 49: 226232 (1976).
Smith, P.G. and R. Doll. Mortality among patients withankylosing spondylitis after a single treatment course with
X-rays. Br. Med. J. 28.1: 449-460 (1982).
Smith, P.G. and AJ. Douglas. Mortality of workers at the
Sellafield plant of British Nudar Fuels. Br. Med. J. 293:
U5-854 (1986).
Spiers, F.W., H.F. Lucas, J. Rundo et al. Leukaernia
incidence in the US dial painters. llcalth Phys. 44 (Suppl.
1): 65-72 (1983).
Stather. J.W., R.fl. Clarke and KP. Duncan. ' h e risk ofchildhood leukaemia near nuclear establishments. NRPBR215 (1988).
Stockwell, H.G., G.11. Lyman, J. Walk et al. Lungcancer in Florida. Risks assodated with residence in thecentral Florida phosphate mining region. Am. J.
Epidemiol. 128. 78-85 (1988).
Stovall, M., SA. Smith and M. Rosenstein. Tssue dases
from radiotherapy of cancer of the uterine cervix. Med
P h p 16: 726-733 (1989).

UNSCEAR 1991 REP(

Svensson, C., G. M u n d and G. Pershagen. Indoor
exposure to radon from the ground and bsonchial cancer
in women. Int. Arch. Occup. Environ. Health 59: 123-131(1987).
S v e w n , C., G. Pcnhgcn and J. Klominck Lungcancer in women and type of dwelling in relation tomdon exposure. Canccr Res. 49: 1861-1865 (1989).
Smith, P.G., It. Doll and E.P. Radford. Cancer mortality
among patients with ankylosing spondylitis not given
X-ray therapy. Br. J. Radiol. 50: 728-734 (1977).
Stram, D.O. and S. Mizuno. Analysis of the DS86 atomic
bomb radiation b i m c t r y methods using data on severe
epilation. RERF TK/1-88 (1988) and Radiat. Res. 117:
93-113 (1989).
S p t o , R. and D.L l'rcston C o d n g for catchment
area non-midency in studies based on tumor-registrydata. RERF CR/1-92 (1992).
Samet, J.M., D.R. Pathak, M.V. Morgan et al. Radonprogeny exposure and lung cancer risk in New Mexim
uranium miners: a casecontrol study. IIealth Phys. 56:415421 (1989).
Samet, J.M.. D.M. Kutvirt and RJ. Waxweiler. Uranium
mining and lung c a m r in Navajo men. N. En$. J. Med.
310: 1481-1484 (1984).
Stidley. C.A. and J.M. Samet. A review of emlogic
studies of lung cancer and indoor radon. Health Phys. 65:
234-251 (1993).
Stjedeldt, M., L. Samuelsson and J. Ludvigsson.
Radiation in dwelling and caner in children. Pediatr.
IIematol. Onml. 4: 55-61 (1987).
Samet, J.M. Radon and lung cancer. J. Natl. Cancer Imt.
81: 745-757 (1989).
Stranden, E. Radon in Norwegian dwelling and thefeasibility of epidemiological studies. Radiat. Environ.
Biophys. 25: 3742 (1986).
Sindair, W.K. Risk. Itesearch and Radiation Protedion.
Radiat. Res. 112: 191-216 (1987).
Stockwell. H.G., C.I. Noss, E.A Ross et al. Lung cancer
and indoor ndon in Florida. Radiat. Prot. h i m . 21:475477 (1988).
Shore-Freedman, E.. C. Abrahams. W. Recant et al.
Neurolemmomas and salivary gland tumours of head andneck in childhood. Cancer 51: 2159-2163 (1993).
Stram, D.O., R. Sposto. D. Preston et al. Stable
chromosome aberrations among A-bomb sunivon: an
update. Radiat. Res. 136: 29-26 (1993).
Sorahan, T. and PJ. Roberts. Chilhood cancer andpaternal exposure to ionizing radiation: preliminary
finding from lhe Oxrod Survey of Childhood Cancers.
Am. J. Ind. Mcd. 23: U3-354 (1993).
Shore, R.E., E.D. Woodard, U.S. Pastemack et al.
Radiation and host factors in human thyroid tumors
following thymus irradiation. Health Phys. 38: 451-465(1980).
Salonen, T. I'rcnatal and pcrinatal factors in childhood
caner. Ann. Qin. Rcs. 7: 27-42 (1976).
Stewart, A and G.W. Kncalc. Radiation dose effects inrelation to obstetric X-rays and childhood cancers. Lancet
1: 1185-1188 (1970).
Smith, P.G. and R. Doll. Mortality from caner and allcauses among British nldiologis~s.Br. J. Radiol. 54: 187194 (1981).

S ' a s , 11. and C.W. Mays. Bone cancers induced by
R'a((Th X ) in children and adults. HeaIth Phyr. 19:
713-729 (1970).
Spiess, M. and C.W. Mays. protraction effect on bonesarcoma indudion of radium-224 in childlen and adults.
p. 437-450 in: Radionudide Camnogenesis. (C.L
Sanders et al., eds.) CONF-720505 (1973).
Spies,
I I., C.W. Mays and D. Chmelevsky. Malignancies
in patients injeded wilh ='Ra. p. 7-12 in: Risks from
Radium and Thorotrast. UIR Report 21. P.M. Taylor etal., eds.) 13ritish lnstitutc of Radiology, London, 1989.
Stebbings, J.11.. 11.F. 1-ucas and AF. Stehney. Mortality
from anccrs of major sites in female radium dial
workers. Am. J. Ind. Med. 5: 435459 (1984).
Swift, M., PJ. Reitnauer, D. M o d l et al. Breast andother cancers in families with ataxia-telangiedasia. N.
Engl. J. Med. 316: 1289-1293(1987).
Stewart, A., W. Pennybacker and R. Barber. Adult
leukaemias and diagnostic x rays. Br. Med. J. 11: 882890(1962).
Spengler, R.F., D.11. Cook, EA. Clarke et al. Cancer
mortality following cardiac calheterization: a preliminary
follow-up study on 4,891 irradiated children. Pediatrics
71: 235-239 (1983).
Shorc, R.E. Radiation epidemiology: old and newchallenges. Environ. Ilealth Peapect 81: 1511.56 (1989).
Shimizu, M., K. Noychi, E. Saircnji et al. Correlation
behveen natural radiation exposure and cancer mortality(5).J. Nihon Univ. Sctl. Dent. 29: 314-320 (1987).
Stevens, W., D.C. 'lhomas, J.L. Lyon et al. Leukemia in
Utah and radimctive fallout from the Nevada test site. J.
An. Mod. Assoc. 264: 585-591 (1990).
Stevens. W., J.E. Till. J.L. Lyon el al. A case-mntrol
study of leukemia deaths in Utah (1952-81) and exposure
to radioactive fallout from the Nevada test site (1952-58).
Final Reprt. National Cancer Institute (1990).
Stebbings, J.H. and W. Semkiw. Central nervous system
tumours and related inlrrlmnial pathologies in radium
dial workers. p. 63-67 in: Risks from Radium andThorotrast. RIR Report 21. (D.M. Taylor et al., eds.)
British Institute of Radiology. London, 1989.
Schoenbcrg. J.B., J.13. Klotz. I1.B. Wilmx et al. Casemntrol study of residential ndon and lung cancer among
New Jersey women. Canccr Res. 50: 6520-6524 (1990).
Stewart, A., J. Webb and D. llewitt. A survey ofchildhood malignancies. Rr. Med. J. 1: 1495-1508(1958).
Sasaki, M.S., S. Saigusa. I. Kimura et al. Biologicaleffectiveness of fision neutrons: energy dependency andits implication for the risk assessment. p. 31-35 in:Proceeding of the International Conferem on Radiation
Effects and Protection, Mito. 1992. Japan Atomic Energy
Research Institute, Tokyo, 1992.
Shore. R.E., N. Ilildrcth. P. Ovoretsky et al. Thyroid
canaer among perso~r?givcn x-ray treatment in infancy
for an enlarged thymu5 gland. Am. J. Epidemiol. 137:
1068-1080 (1993).
Spsto, R., D.O. Stmm and A.A. Awa. An estimate of
the magnitude of rdndom errors in the DS86 dosimetryfron~ data on chromosome aberrations and severe
epilation. Radiat. Rcs. 128: 157-169 (1991).
Straume, T., S.D. Egbert, WA. Woolson et al. Neutron
discrepancies in the 11S86 Iliroshima dosimetry system.
tlei~lthPhys. 63: 421-426 (1992).

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557

S58

S59

S60

S61

S62
S63

S64

S65

h
c
,J., L. TwdSek, E. Kunz ct al. A survey of theaechoslovak follow-up of lung cancer mortality inuranium miners. Ilealth Phys. 64: 355-369 (1993).
Samet, J.M., S.R. Pathak, M.V. Morgan et al. Lungcancer mortality and exposure to radon progeny in acohort of New Mexico underground uranium miners.
tlealth Phys. 61: 745-752 (1991).
Swift, M., D. Morrell. R.B. Massey et al. I n c i d e w ofcancer in 161 families affected by ataxia-telangieotasia.
N. Engl. J. Mcd. 325: 1831-1836 (1991) andcorrespondence regarding this subjed by variols authors
and reply by M. Swift et al. in: N. Engl. J. Med. 326:
1357-1361 (1992).
Storm, lI.F1., M. Andenson. J.D. Boice et al. Adjuvant
radiotherapy and risk of contralateral beast cancer. J.
Natl. Cancer Inst 8 4 1245-1250 (1992).
Shore, R.E. lssua and epidemiological evidence
regarding radiation-induced thyroid cancer. Radiat Res.
131: 98-111 (1992).
Shore, R.E. Overview of radiation-induced skin cancer inhumans. Int. J. Radiat. Biol. 57: 809-827 (1990).
Scfineider, AB.. E. Ron, J. Lubin et al. Dose-response
relatiomhips for radiation-induced thyroid cancer andthyroid noddo: evidence for the prolonged effeds ofradiation on the thyroid. J. a i n . Endocrinol. Metab. 7 7362-364 (1993).
bmi4,M., J. Scvc and J. Thomas. Alpha irradiation of
the skin and the possibility of late effects. Health Phys.
35: 803-806 (1978).
Shimizu, Y.. H. Kato and W.J. Schull. Dose-response
analysis of atomic bomb survivors exposed to low-level
radiation. p. 3-4 in: REIW Update. Autumn (1992).
Sposto, R., D.L. Preston, Y. Shimizu et al. The effecl of
diagnostic misdassificttion on noncancer and cancer
mortality dose responsc in the RERF Life Span Study.
Biomctrio 48: 605417 (1992).
Sindair, W.K Experimental RBE values of high-LET
radiations at low doses and the implications for quality
factor assignment. Radiat. Prot. Dosim. 13: 319-326(1985).
Sindair. W.K. J.D. A b b n , H.E. Farnn et al. A
quantitative autoradiographic study of radioactive
distribution and dosage in human thyroid glands. Br. J.
Radid. 29: 3641 (1956).
Shimizu, Y., WJ. Schull and 11. Kato. Cancer risk among
atomic bomb survivors. J. Am. Med. hssoc. 264 (5):601404 (1990).
Shigematsu, 1. and J.W. Thicsen. Childhood thyroid
cancer in Relam. Nature 359: 681 (1992).
Strong, L.C. Genetic and environmental interactions.
(3an~er40: 1861-1866 (1977).
Straume, T., W.Ilarris, A.A. Marchetti et al. Neutrons
confirmed in Nagasaki and at the Army Pulsed Reactor
Facility: implications for Iliroshima. Radiat. Res. 138:
193-200 (1994).
Samct, J.M., J. Stolwijk and S.L. Rose. Summary:international workshop on residential Rn epidemiology.
Health Phys. 60.223-227 (1991).
Taylor, D.M., C.W. Mays, G.R. Gerbcr ct al. (eds.).
Risks from Radium and 'Ihorotrast. B1K Report 21.
British Institute of Radiology, London, 1989.

181

Tokunaga, M., CE. Land, T. Yamamoto et al. Incidenceof female breast cancer among atomic bomb survivors,
Hiroshima and Nagasaki, 1950-1980. RERF 'IlUl584
and Radiat. Res. 112: 243-272 (1987).
T3 Tomaek, L., S.C. Darby, T. Feam et al. Patterns of lungcancer mortality among uranium miners in West Bohcmia
with varying rates of exposure to radon gas. Radiat. Rcs.
137: 251-261 (1994).
T4 Travis, L.B., C.E. Rochelle, J.D. Boicz Jr. et al. Seamd
cancers following non-llodgkin's lymphoma. C a n e r 67:
2002-2009 (1991).
T5 Tucker, M.A, A T . Meadows. P. Morris Jones et al.
Therapeutic radiation at young age linked to secondary
thyroid cancer. Proc. Am. Soc a i n . Omol. 5: 827(Abstract) (1986).
T6 Tucker, M A , GJ. D'Angio, J.D. Boice Jr. et al. Bones a m m a s linked to radiotherapy and chemo-therapy inchildren. N. Engl. J. Mcd. 317: 588-593 (1987).
T7 Tucker, M A , A.T. Meadows, J.D. Boice et al. Leukaemia after therapy with alkylating agents for childhood
cancer. J. Natl. Cancer Imt. 78: 459-464 (1987).
T8 Tucker, M A . C.N. Coleman. R.S. Cox et al. Risk of
second cancers after treatment for Hodgkin's disease. N.
Engl. J. Med. 318: 76-81 (1988).
Tom&k, L., S.C. Darby, AJ. Swerdlow et al. Radon'I9
exposure and cancers other than lung cancer among
uranium miners in West Bohemia. Lancet 341: 919-923(1993).
no Tinnarche, M., A. Raphalan, F. Allin et al. Mortality of acohort of French uranium miners exposed to relatively low
radon concentrations. Br. J. C a m 67: 1090-1097 (1993).
TI1 Teppo, I-., E. Pukkala and E. SaxBn. Multiple cancer - anepidemiologic excrase in Finland. J. Natl. Cancer Imt.
75: 207-217 (1985).
'I'12 Tirmarche, M., A. Rannou, A. Mollie et al. hidemiological study of regional cdncer mortality in France andnatural radiation. Radiat. Prot. Dosim. 24: 479-482(1988).
T13 Tucker. M.A, J.D. Boice Jr. and D.A Iloffman. *nd
c a m r following cutaneous melanoma and caners of thebrain, thyroid, connedive tissue, bone, and eye in
Comedicuf 1935-82. Natl. Cancer Inst. Monogr. 68:
161-189 (1985).
Tl4 Thomas, D., S.C Darby, F. Rgnani et al. Definition andestimation of lifetime detriment from radiation exposures:principle. and methods. Health P h p . 63: 259-272 (1992).
Tl5 Thompson, D.E.. K Mabuchi, E Ron et al.
incidence in atomic bomb survivors. Part 11: Solid tumors,
1958437. RERF TR/5-92 (1992) and Radiat. Res. 137:
S17-S67 (1994).
T16 Taylor, J A , M.A. Watson, T.R. Deverew et al. p53
mutation hotspots in radon-associated lung cancer. Lancet
343: 86-87 (1994).
U1 United Nations. S o u r m and meds of Ionizing
Radiation. United Nations Scientific Committee on the
FXects 01Atomic Radiation. 1993 Report to the General
Assembly, with saenlific annexes. United Nations sales
publication E.94.K.2. Unitcd N;16ons. Ncw York, 1993.
U2 United Nations. S o u r m , Elfcds and Risks of Ionizing
Radiation. United Nations Sdentific Committee on Ihe
Efftxts of Atomic Radiation, 1988 Report to the General
Asscrnbly, with anncxcs. United Nations sales publication
E.88.R.7. United Nations, New York. 1988.

T2

1994 REPORTU3

United Nations. Genetic and Somatic Effects of Ionizing
Radiation. United Nations Scientific Committee on theWccts of Atomic Radiation, 1986 Report to the General
Assembly, with annexes. United Nations sales puMication
E.86.U.9. United Nations, New York, 1986.
U4 United Natiom. Ionizing Radiation: Sources andBiological Effects. United Nations Scientific Committee
on the Effects of Atomic Radiation, 1982 Report to theGeneral Assembly, with annexes. United Nations sales
publication E.82.1X.8. United Nations, New York, 1982.
US United Nations. Sourccs and Effeds of Ionizing
Radiation. United Nations Sdentific Committee on the
Effects of Aomic Radiation, 19n Report to the General
Assembly, with annexes. Unikd Nations sales puMication
E.77.IX.1. United Nations, New York, 1977.
U6 United Nations. Ionizing Radiation: Levels and Effeds.
Volume I: Levels. Volume 11: Effects. United Natiom
Scientific Committee on the Effeas of Atomic Radiation,
1972 Report to the General Assembly, with annexes.
United Nations sales publication E.R.IX.17 and 18.
United Nations, New York, 19?2.
U12 Upton, k C Risk estimates for oramgenic effects ofradiation. p. 1-29 in: Risks Assodated with Ionising
Radiation. Annals of the lCRP 22. Pergamon Press,
Oxford, 1991.
U13 Urquhart, J.D., RJ. Black, MJ. Muirkad et al. Casemntrol study of leukaemia and non-Hodgkin's lymphoma
in children in Caithncss ncar the Dounreay nudear
installation. Br. Med. J. 302: 687-692 (1991).
U14 Ullrich, R.L. and R.J. Preston. Mycloid leukaemia inmale R1;U mice following irradiation with fission
spedmm neutrons or y rays. Radiat. Res. 109: 165-170(1987).
V1 van Kaick, G., 11. Muth, A. Kaul et al. Results of theGerman Thorotrast study. p. 253-262 in: Radiation
Carcinogenesis: Epidemiology and BiologicalSignificance. (J.D. Boice Jr. and J.F. Fraumeni Jr., eds.)
Raven Press, New York, 1984.
X? van Kaick, G., H. Muth, k Kaul et al. Report on theGerman Xrotrast study. Strahlentherapie (Suppl.) 80:
114-118 (1986).
W Vaughan, J. Cardnogenic effects of radiation on thehuman skeleton and supporting tissues. p. 311-334 in:Radiation Carcinogenesis. ( k c U p n et al., eds.)
Usevier Ress, New York, 1986.
V4 Vaeth, M. and D A Pierce. Calculating exass lifetime
risk in dative risk models. Environ. f Iealth Persped. 87:
83-94 (1990) and RERI: CRn-89 (1989).
V5 Voelz, G.L.. R.S. Gricr and LH. Hempelmann. A 37year medical follow-up of Manhattan project Pu workers.
11~4thPhys. 48: 249-259 (1985).
V6 Vwlz, G.L.. G.S. Wilkinson, J.W. Healy et al. Mortality
study of Los Namos workers with higher exposures toplulonium. p. 318-327 in: Epidemiology Applied toIIealth Physics. CONF-830101 (1983).
V7 Voelz, G.L., A.R. Steverson and C.C. Stewart. A 42-year
medical follow-up of Manhattan project plutonium
workers. Ileallh Phys. 56 (Suppl. 1): S46 (1989).
V8 Valapsa, P., A Santom, F. Fossati-Bcllani d al. Second
acute leukemia and other malignancies following
treatment for llodgkin's disease. J. a i n . Oncol. 4: 8 M
837 (1986).

van Kaick, G., 14. Wcsch, H. Liihrs et al. The German
thorotrast study - report on 20 yean follow-up. p. 98-104
in: Risks from Radium and Thorotrast. BIR Report 21.
(D.M. Taylor et al., eds.) British Institute of Radiology,
London, 1989.
V10 Viel, J.F. and S.T. Richardson. Childhood leukaemia
around the La IIague nuclear waste reprocessing plant
Br. Med. J. 300:580-581 (1990).
V11 Voelz, G.L. and J.N.P. Lawrerxz. ,442-y medical followup of Manhattan project plutonium workers. Health Phys.
61: 181-190 (1991).
V12 Vaeth, M. Some statistical issues important to future
developments in human radiation research. p. 161-164 in:
The Future of Human Radiation Research. BR Report
22. (G.B. Gerber, D.M. Taylor, E. C a d i et al.. eds.)
British Institute of Radiology, London, 1992.
V13 Vomtille, W.T. and 11.1-A Sacatello. Radon and canczr.
J. Environ. Health 53: 25-28 (1990).
V14 Vaeth, M., D.L. Preston and K. Mabochi. The shape ofthe cancer incidence dose-response arve for the A-bomb
survivors. p. 75-79 in: Low Dose Irradiation and
Biological Defense Mechanisms. Elsevier Science
Publishers, Amsterdam, 1992.
W1 Woodward, A, D. Rodu, AJ. McMichael et al. Radon
exposures at the Radium I-fill uranium mine and lungcancer rates among former worken, 1952-1987. Cancer
Causes Conlrol 2: 213-220 (1991).
W2 Walter, S.D., J.W. Meigs and J.F. Heston. The
relationship of can- incidenoc to terrestrial radiation andpopulation density in C o n d c l ~ t ,1935-1974. Am. J.
Epiden~iol.123: 1-14 (1986).
W3 Wing, S., C.M. Shy, J.L. Wood et al. Job fadors, radiation and cancer mortality at OKNL: follow-up through1984. Am. J. Ind. Med. 23: 265-279 (1993).
W4 Wick, R.R. and W. Giissner. Follow-up study of lateeffects in Radium-224 treated ankylosing spondylitis
patients. Ilealth Phys. 44 (Suppl. 1): 187-195 (1983).
WS Wick, R.R., D. Qunelevsky and W. G h n e r . Radium224: risk to bone and haematopoietic tissue in ankylosing
spondylitis patients. p. 3 8 4 in: The Radiobiology of
Radium and Thorotnst. (W. W n e r et al., eds.)Urban
and Schwarzenberg, Munchen. 1986.
W6 Wilkjnson, G.S. Gastric c a n m in New Mexim munties
with significant deposits of uranium. Arch. Envimn
Health 40: 307-312 (1985).
W7 Wilkinson. GS., G.L. lietjen, L.D. Wiggs a al. Mortality
among plutonium and other radiation workers at a plutonium wcapom facility. Am. J. Epidemiol. 125: 231-250(1987).
W8 Wang, J. Statistical analysis of cancer mortality data ofhigh background radiation areas in Yiangjiang. Chin. J.
Radiol. Med. Prot. 13: 291-294 and 358 (1993).
W9 Whittemore, A.S. and A McMillan. Lung cancer
mortality among U.S. uranium miners: a reappraisal. J.
Natl. Cancer Inst. 71: 489499 (1983).
W10 Wang, J.X., J.D. Boim Jr., BX. Li et al. Cancer among
medical diagnostic X-ray workers in China. J. Natl.
Cancer Inst. 80: 344-350 (1988).
W11 Wesch, II., W. Kiedel, K Hasenohrl et al. German
thorotrast study: results of the long-term animal studies
on the effect of incorporated radioadive andnonradioadive particles. S~rahlentherapie(Suppl.) 80.
186-188 (1986).
V9

ANNEX A: EPIDEMIOLOGICAL STUDIES OF RADIATION CARCINOGENESIS

183

W22 Wemer, M.M. and D.K. Mym. Causes of death among
W12 Wesch, H., G. van Kaick, W. Riedel et al. Recent results
long-term employees of Chalk River laboratories, 1966of the German thorotrast study - statistical evaluation of
1989. AIZCL-10293 (1990).
animal experiments with regard to the nonradiation
W23 Wigs, L.D., C A Cox-DeVore and G.L. V d zeffects in human thorotrastasis. Health Phys. 44 (Suppl.
Mortality among a cohort of workers monitored for1): 317-321 (1983).
exposure to the radiation isotope 210-polonium: 1944W13 Wiggs, L.D., C A Cox-DeVore and G.L. Voelz.
1972. flealth Phys. 61: 71-76 (1991).
Mortality among a cohort ofworkcn monitored for 2 1 0 ~ ~W24 Wiggs, L.D., CA. Cox-DeVore, G.L. Voelz et al.
expure: 1944-1972. Health Phys. 61: 71-76 (1991).
to external ionizing
Mortality among workers ex@
W14 Wang, JX., P.D. Inskip, J.D. Boice Jr. et al. Canox
radiation at a nudear facility in Ohio. J. of Occup. Med.
inadence among medical diagnostic x-ray workcrs in
33: 632437 (1991).
China, 1950 to 1985. Int. J. Cancer 45: 889-895 (1990).
X1 Xuan, X.Z, J.H. Lubin, J.Y. Li et al. A mhort study in
W15 Wei, L., Y. Zba, Z. Tao et al. Epidemiologicalsouthern China of tin miners exposed to radon and radon
investigation of radiological effwts in high backgrounddecay produds. Health Phys. 64: 120-131 (1993).
radiation areas of Yiangjiang, China. J. Radiat. Res. 31:
Y1 Yoshimoto, Y., M. Soda, WJ. Schull et al. Studies of
119-136 (1990).
children in utcro during atomic bomb detonations. in:
W16 Wei, L, Y. Zha, 2.Tao et al. Cancer mortality study inProceeding of the 203rd National Meeting of the Amerihigh background radiation areas of Yiangjiang, China.
can Chemical Society, 1992, San Francisco. American
Radiat. Biol. Res. Commun. 23: 209-220 (1988).
Chemical Society, Washington D.C. (1994, in press).
W17 Wang, Z., J.D. Boicz Jr., L. Wei el al. Thyroid nodularity
Y2 Yoshimoto, Y., 11. Kato and WJ. Schull. Risk of cancer
and chromosome aberrations among women in areas ofamong children exposed in utero to A-bomb radiations,high background radiation in China. J. Natl. Cancer Inst.
1950-84. RERF m4-88(1988) and Iancet ii: 665-669
82: 4 7 8 4 (1990).
(1988).
W18 Wick, R.R. and W. Gssner. Recent results of the iollowY3 Yoshimoto, Y., J.V. Neel, WJ. Schull et al. Malignant
up of radium-224-treated ankylosing spondyli tis patients.
tumors during the first two decades of life in thep. 25-28 in: Risks from Radium and Thorotrast. BIR
offspring of atomic bomb survivors. RERF W4-90
Report 21. P.M. Taylor et al., eds.) British Institute of(1990) and Am. J. Hum. Genet 46: 1041-1052 (1990).
Radiology, London, 1989.
Y4 Yoshimoto, Y., WJ. Schull, H. Kato et al. Mortality
W19 Waxweiler, RJ., V.E. Archer. RJ. Roscoe et al. Mortality
among the oifspring (F,) of atomic bomb survivors,
patiems among a retrospective cohort of uranium mill
1946-85. RERF TRJ1-91 (1991) and J. RadiaL Res. 32:
workers. p. 428435 in: Epidemiology Applied to Health327-351 (1991).
Physics. CONF-830101 (1983).
Y5 Yoshimoto, Y. Cancer risk among children of atomic
W20 Wing, S., CM. Shy, J.L. Wood ct al. Reply to comments
bomb survivors. A review of RERF epidemiological
by Gilbert and Prichard. llealth Phys. 62: 261-264
studies. J. Am. Med. Arsoc. 264(5): 596400 (1990).
(1992).
Y6 Yao, X.S., J.H. Lubin, Y.L. Qiao et al. Radon progeny
W21 Wing, S., C.M. Shy, J.L. Wood et al. Mortality among
exposure, tobacco use and lung cancer in Chinese tin
workers at Oak Ridge national laboratory. J. Am. Med.
miners. Radiat. Res. 138: 326-336 (1994).
Assoc. 265: 1397-1402 (1991).