RADIATION RESEARCH 159, 228–238 (2003)

0033-7587/03 $5.00
q 2003 by Radiation Research Society.
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Second Analysis of Mortality of Nuclear Industry Workers in Japan,
1986–1997
Tamiko Iwasaki,a,e Motoi Murata,a,1 Sumio Ohshima,a Toshio Miyake,a Shin-ichi Kudo,a Yasushi Inoue,a Minoru Narita,aTakesumi Yoshimura,b Suminori Akiba,c Toshiro Tango,d Yasuhiko Yoshimoto,e Yukiko Shimizu,f Tomotaka Sobue,gShizuyo Kusumi,a Chikao Yamagishia and Hiromichi MatsudairaaaRadiation Effects Association, Kajicho, Chiyodaku, Tokyo, 101-0044, Japan; b University of Occupational and Environmental Health, 1-1
Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; c Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan; d National
Institute of Public Health, 3-6, Minami 2, Wako, 351-0197, Japan; e National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba,263-8555, Japan; f Radiation Effects Research Foundation, 5-2, Hijiyama Park, Minami-ku, Hiroshima, 732-0815, Japan; and g National Cancer
Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

International Commission on Radiological Protection (1).
The risk estimates adopted in the recommendations rely inpart on epidemiological studies of atomic bomb survivors
in Hiroshima and Nagasaki who were exposed to high doses of acute radiation (2). It was assumed that the findings
on cancer mortality from those studies could be extrapolated to low-dose and low-dose-rate radiation exposureswith some modifications. However, considerable uncertainties are associated with that extrapolation process, because
the biological mechanisms of radiation carcinogenesis arestill not well understood (3). It is thus important to provide
a basis for the adequacy of current radiation protection
measures, at least for radiation workers, in terms of thehealth effects of low-level radiation.
A number of epidemiological studies of nuclear industry
workers have been undertaken to obtain information on thehealth effects of low-dose and low-dose-rate radiation exposure (4–21). In Japan, the Institute of Radiation Epidemiology (IRE) of the Radiation Effects Association (REA)
initiated a cohort study of nuclear industry workers in 1990.
The Ministry of Education, Culture, Sports, Science andTechnology (MEXT) of Japan had entrusted this study to
REA. The results of the first analysis, dealing with observations for the period 1986–1992, were reported previously(17). The present report presents the results of the second
analysis with extension of the observation period to 1997
and with a larger number of study subjects.

Iwasaki, T., Murata, M., Ohshima, S., Miyake, T., Kudo,
S., Inoue, Y., Narita, M., Yoshimura, T., Akiba, S., Tango, T.,
Yoshimoto, Y., Shimizu, Y., Sobue, T., Kusumi, S., Yamagishi,
C. and Matsudaira, H. Second Analysis of Mortality of Nuclear Industry Workers in Japan, 1986–1997. Radiat. Res. 159,
228–238 (2003).
A cohort study of nuclear industry workers was initiated in1990 to determine the possible health effects of low-level radiation. A total of 5,527 deaths were ascertained among 176,000
male workers who had been retrospectively and/or prospectively
followed for an average of 7.9 years during the observation period 1986–1997. Statistical analyses were made mainly on theprospective follow-up outcome of 120,000 workers followed foran average of 4.5 years. The standardized mortality ratio (andits 95% confidence interval) was 0.94 (0.90, 0.97) for 2,934 casesof all causes combined and 0.86 (0.82, 0.91) for 1,305 cases of
non-malignant diseases combined, which suggested a healthy
worker effect. For 1,191 cases of all cancers combined, it was
0.98 (0.93, 1.04), indicating no difference in mortality from thatof the general population. In tests for trend of death rate withincreasing radiation dose, no significant correlation was foundfor all cancers combined. For site-specific cancers, most cancers
including leukemia showed no positive correlation with dose, except for cancers of the esophagus, stomach and rectum and multiple myeloma. External causes showed a significant correlation
with dose. A separate questionnaire study indicated that these
positive findings could be ascribed in part to lifestyle characteristics of the workers. For leukemia only, we attempted to estimate the excess relative risk per unit dose of radiation, which,with reservations because of its wide confidence interval, waswithin the range of variation of the risks reported in other radiation epidemiological studies. This population must be studied
for a longer time and with a consideration of the possible effectsof confounding factors. q 2003 by Radiation Research Society

MATERIALS AND METHODSThis study was reviewed and approved by the Research Ethics Committee and conformed to the Guidelines for Ethics of EpidemiologicalStudy of the Japanese government.

INTRODUCTION
Population and Follow-up of Vital Status

Current radiation protection standards throughout theworld are based largely upon the recommendations of the

In Japan, a registry system of radiation workers at nuclear facilities
was established in 1977 that is operated by the Radiation Dose Registration Center (RADREC) of REA. Its operational system and database ofdose records were described in detail in the previous paper (17). The
present follow-up study was based upon approximately 244,000 radiation

1
Address for correspondence: Institute of Radiation Epidemiology, Radiation Effects Association, 1-9-16, Kaji-cho, Chiyoda-ku, Tokyo 1010044, Japan; e-mail: mmurata@rea.or.jp.

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workers, including 242,000 males and 2,000 females, who were registered
by RADREC as of the end of March 1995 and who satisfied certain
requirements such as having a record of exposure dose and Japanesenationality. Compared to our first report (17), which dealt with 184,000
workers registered by RADREC as of March 1989, the present study was
supplemented by about 60,000 workers, consisting of those who worked
only at fuel-processing plants that were excluded from the previous analysis (about 4,000) and those who had first engaged in radiation work after
March 1989 (about 56,000).
The requirement of Japanese nationality was set to use residence registration cards (RRC) for follow-up studies. In Japan, every municipality
maintains RRC of residents, including their name, date of birth, gender,
address, first date of residence, and previous address. If any resident diesor moves to another municipality, the RRC is updated with the date ofdeath or relocation and the next address in the case of relocation and ismaintained for exactly 5 years, after which it is deleted from the registration file.
For the follow-up of study subjects, personal identification information
was first provided by RADREC, including their central registration number, name, gender and date of birth. Next, their residence address information was obtained with the cooperation of the nuclear facilities atwhich they worked. Then copies of RRC were acquired from the respective local government offices to ascertain the vital status of the study
subjects. Because of the limited period of maintenance of RRC for those
who died or emigrated, follow-up checks must be continued at intervalsof less than 5 years, since those who have died or emigrated would be
lost from the study population otherwise.
Using RRC, the cohort can be followed up both retrospectively andprospectively. For the retrospective observations, the initial date was determined by taking the later of either April 1 of the first year of engagement in radiation work or the date 5 years preceding the date when the
RRC was acquired at the first follow-up. Since this follow-up study started in 1991, the earliest year of observation would be 1986. The end of
the retrospective observation period was the date when the RRC was firstacquired. Among the total population of 244,000 workers, approximately
177,000 (72.6%) were followed up successfully. The remaining workers
were lost due to either imprecise address information provided by therespective nuclear facilities or expiration of the storage period of the RRC
at the respective municipal offices for deaths or relocations that had occurred prior to the first follow-up.
Prospective follow-up was made for about 120,000 workers who wereconfirmed to be alive at time of the first follow-up. Thus the initial dateof the prospective observation period was the date when the RRC had
first been acquired. The terminal date was the date when the RRC had
been obtained in the most recent follow-up, the date of death or relocation, or the date of dropout from the study due to failure of follow-up,
whenever these events occurred earlier than the closing date of the observation period, i.e. December 31, 1997. Otherwise, this latter date was
the terminal date. The dropout rate was only 0.3% of the population, andthe majority of this resulted from those who had emigrated from a certain
municipality but who for some unknown reason could not be confirmed
to have settled successfully in the municipality given as the destinationof relocation.
For those whose death was ascertained from the RRC, the cause ofdeath was obtained by record linkage with magnetic tape copies of vitalstatistics death records (for the period 1986–1997) provided by the Ministry of Health, Labor and Welfare of Japan. Indices used for record
linkage were the date of birth, date of death, sex and municipality ofresidence. Iwasaki et al. (22) reported successful determination of causesof death by means of this record linkage in 99.7% of subjects.
Radiation Dose Records
The effective dose data registered at RADREC were used to determine
the cumulative doses of subject workers. Dosimetry records of radiation
workers are prepared by the respective nuclear facilities for the purposeof radiation protection management, and exposure doses are reported to229

RADREC each year as the annual (mSv), external and internal doses
combined. Internal doses were almost negligible. Film badge dosimeters
and, especially in recent years, thermoluminescence dosimeters were used
for determination of external radiation doses. Doses below the detectablelevel, which was around 0.1 mSv for g rays but was slightly variable
depending on the different types of dosimeters, were reported to RADREC as x values. Such doses were counted as 0 mSv in this study. For
dose records missing for such reasons as the loss of dosimeters, the respective facility made estimates of dose based on certain predetermined
rules, such as use of measurement by a supplementary dosimeter or useof dosimeters of other workers who had engaged in work at the sametime.
Although RADREC initiated the registration in 1978, earlier dosimetry
records of workers had been maintained at the respective nuclear facilities
back to 1957, and these were provided to RADREC. Consequently, dose
data available for this study cover the period from 1957 to 1997; thesedata were used to calculate the cumulative radiation doses for individual
workers. The average annual dose per person has gradually decreased
over the years, from about 3.5 mSv before 1982 to about 1.2 mSv after
1990, which is ascribable mainly to technical improvements in procedures
to reduce the radiation exposure of workers.
Dose records filed in RADREC reflect changes over time in the definition of radiation quantities and units, advances in the methods of dose
measurement and evaluation of dose, and methodological differences between the respective nuclear facilities. The Radiation Dosimetry Committee was organized to investigate and examine from an expert viewpoint the problems involving radiation control practices and the methodsof dose measurement and evaluation. The investigations and assessments
were carried out based on the results of a questionnaire survey and onsite inspections of all nuclear facilities, and also by taking into consideration various pertinent technical materials. The results of these examinations indicated that the quality of the dose records was adequate andproper for use in this epidemiological study, as described in the previous
report (17).
Characteristics of the Study Populations
Since the follow-up of the cohort population was made both retrospectively and prospectively, the following two study populations wereselected for the statistical analysis. First was the total study population,
consisting of approximately 176,000 male workers whose vital status had
been verified through either retrospective or prospective follow-up for theperiod 1986–1997. From this population, approximately 119,000 workers
who had been followed up prospectively for the period 1991–1997 wereseparated and designated as the prospective study population. All of theremaining workers (about 57,000) were those subjects who had been
added to the cohort population subsequent to the first analysis. Female
workers were excluded from the study populations because they were too
few in number, i.e. about 950.
Because follow-up was begun retrospectively by use of RRC in thisstudy, there is no fixed single starting point common for all subjects inthe population. Thus Table 1 shows the distribution of the birth years of
the study subjects instead of their age distribution at the start of thefollow-up. The birth year ranged from 1903 to 1977, thus covering morethan 70 years. It appears that the distribution is skewed slightly to later
years in the total study population compared to the prospective study
population, reflecting the fact that the former population had a larger
proportion of those recently engaged in work than the latter.
Table 2 shows the distribution of cumulative doses by the end of 1997
in both the total and prospective study populations. Among those classified in the ,10-mSv dose class, the dose values for 41% of the total
and 38% of the prospective study populations were actually below thedetectable level (0 mSv). In 17% of those in the 1001 mSv group, thedose exceeded 200 mSv but was less than 450 mSv. For the total study
population, the mean cumulative dose per person was approximately 12.0
mSv and the population dose was about 2,109 person-Sv. The mean cumulative dose per person in the prospective study population was ap-

230

IWASAKI ET AL.

TABLE 1
Distribution of Birth Years in the
Study Populations

TABLE 2Distribution of Cumulative Doses to the End of
1997 in the Study Populations.

Birth years

Total study
population
Number (%)

Prospective study
population
Number (%)

1919a
1920–1929
1930–1939
1940–1949
1950–1959
1960–19691970–bTotal

1,300 (0.7)
9,078 (5.2)
26,105 (14.8)
42,775 (24.3)
46,962 (26.7)
36,745 (20.9)
12,974 (7.4)
175,939 (100)

1,055 (0.9)
7,936 (6.6)
20,661 (17.3)
33,171 (27.8)
35,753 (29.9)
20,681 (17.3)
227 (0.2)
119,484 (100)Cumulative
dose
groups
(mSv)
,10
10–20
20–50
50–100
1001b
Total
a

a
Four percent of total and 1% of prospective study populations wereborn earlier than 1910 and the earliest birth year was 1903.
b
The latest birth year was 1977.

proximately 15.3 mSv and the population dose was about 1,826 personSv. The difference in mean cumulative dose between the total and prospective study populations reflects the larger proportion of persons in theformer group who had recently become engaged in radiation work.
The distributions of calendar year of first engagement in radiation workand length of employment in radiation work in the different dose groups
as of the end of 1997 are shown in Tables 3 and 4, respectively, for only
the prospective study population. It appears that the higher the cumulative
dose, the larger is the percentage who started radiation work in earlier
years as well as the percentage who had been working for longer times.
The latest place of residence of study subjects during the observation
period was classified into eight major districts from north to south; theirdistribution in the individual dose groups is shown in Table 5 only forthe prospective study population. A large difference in the residence area
was observed among the indicated dose groups with statistical significance (P , 0.0001 by x2 test). Among the eight districts, Kanto was themost common area of residence in lower-dose classes, whereas in thehigher-dose classes, residents of Hokkaido and Tohoku, and Hokuriku
areas were more common.
The average observation period was 7.9 years per person for the
175,939 workers in the total study population (retrospective and prospective follow-up subjects) and thus generated 1.39 million personyears. In the prospective study population, the average observation period
for the 119,484 workers was about 4.5 years per person and thus generated 0.54 million person-years. The mean age at the end of observation
period was 45.7 and 49.1 years for the total and prospective study populations, respectively.
Statistical Analysis
Both external and internal comparisons were made using methods similar to those of other radiation epidemiology studies (4–21). The total

Prospective study
population

Total study population

Number (%)

Meancumulative
dose
(mSv)

Number (%)

Meancumulative
dose
(mSv)

131,809 (74.9)
16,309 (9.3)
16,270 (9.2)
7,390 (4.2)
4,161 (2.4)
175,939 (100)

1.6
14.3
31.6
69.8
154.0
12.0

83,220 (69.6)
12,421 (10.4)
13,197 (11.0)
6,641 (5.6)
4,005 (3.4)
119,484 (100)

1.7
14.4
31.9
70.2
154.7
15.3

a
Of this class, 41% in the total and 38% in the prospective study
populations had 0 mSv exposure.
b
Of this class, 17% exceeded 200 mSv, but received less than 450
mSv.

observation period was divided into three calendar-year periods (1986–
1989, 1990–1994 and 1995–1997), and the total age range (20 to 84
years) was stratified into 5-year age classes (20–24, 25–29, . . . , 80–84).
Observed person-years were calculated separately for each age class byeach observation period. Person-years for those over 84 years old were
excluded because death certificate diagnosis of causes of death is generally less reliable at older ages. Causes of deaths of interest in this study
were primarily all cancers and site-specific cancers, but they also included
all causes, non-neoplastic diseases and external causes.
In the external comparison, the standardized mortality ratio (SMR) andits 95% confidence interval (CI) were calculated compared to the general
Japanese male population. The SMR is the ratio of observed to expected
number of deaths (23). The expected number of deaths was calculated
by applying the mortality rates of the general Japanese male population
in individual age classes and calendar-year periods as described above tothe corresponding person-years of the study population.
In the internal comparison, a one-sided trend analysis with z values
was performed (23). Namely, the study population was divided into fivegroups by cumulative dose levels, i.e. less than 10, 10–20, 20–50, 50–
100 and 100 mSv or more, and the data were tested for whether the ratioof observed (O) to expected (E) number of deaths (O/E ratio) in individual dose groups was increased significantly with increasing cumulative
dose. Mean cumulative doses over the respective person-years were usedas the scores of individual dose groups. When calculating the expected
number of deaths, it was standardized to the mortality of the total population, in addition to the above-mentioned age classes and calendar-year
periods. The residence area was also adjusted for by the classification
shown in Table 5.
As was seen in the previous section, this population was heterogeneous

TABLE 3Distribution of Calendar Year of First Engagement in Radiation Work in Different Dose Groups as of the Endof 1997 in the Prospective Study Population
Dose group (mSv)
Years
–1974
1975–
1980–
1985–
Total
a

,10
9,763 (11.7)
20,660 (24.8)
29,238 (35.1)
23,559 (28.3)
83,220 (100.0)

Percentage in parentheses.

a

10–20

20–50

50–100

1001

Total

1,674 (13.5)
3,851 (31.0)
4,553 (36.7)
2,343 (18.9)
12,421 (100.0)

2,066 (15.7)
4,225 (32.0)
4,755 (36.0)
2,151 (16.3)
13,197 (100.0)

1,309 (19.7)
2,301 (34.6)
2,244 (33.8)
787 (11.9)
6,641 (100.0)

1,063 (26.5)
1,580 (39.5)
1,132 (28.3)
230 (5.7)
4,005 (100.0)

15,875 (13.3)
32,617 (27.3)
41,922 (35.1)
29,070 (24.3)
119,484 (100.0)

231

MORTALITY OF NUCLEAR INDUSTRY WORKERS IN JAPANTABLE 4
Distribution of Duration of Employment in Radiation Work in Different Dose Groups as of the End of 1997
Dose group (mSv)

Period(years)

,10

10–20

20–50

50–100

1001

Total

1
2–4
5–9
101
Total

28,820 (34.6)a18,367 (22.1)
11,507 (13.8)
24,526 (29.5)
83,220 (100.0)

1,843 (14.8)
2,786 (22.4)
1,916 (15.4)
5,876 (47.3)
12,421 (100.0)

289 (2.2)
2,191 (16.6)
2,443 (18.5)
8,274 (62.7)
13,197 (100.0)

0 (0.0)178 (2.7)
939 (14.1)
5,524 (83.2)
6,641 (100.0)

0 (0.0)1 (0.0)160 (4.0)
3,844 (96.0)
4,005 (100.0)

30,952 (25.9)
23,523 (19.7)
16,965 (14.2)
48,044 (40.2)
119,484 (100.0)aPercentage in parentheses.

with respect to various characteristics, such as starting age and starting
year of radiation work, duration of engagement in work, residence areaand so forth (Tables 3–5), and some of these factors were potential confounding factors in the present study. Among these characteristics, at least
residence area would probably be associated with mortality of the study
subjects, since a geographic variation in mortality is well known for various kinds of cancer in Japan (24). Although it would be better to choose
the place of residence in the earlier or main part of life of individuals asa confounder, such information was not available because of the shortlength of the present follow-up period. We therefore decided to include
the latest residence as a potential confounder in the internal comparison.
The other factors, though they may also be associated with the mortalityof the study subjects, were not adopted as controlling factors simply
because the observation period was still too short to adjust for these timedependent factors in the analysis.
The internal comparison was performed in two ways, either with orwithout consideration of the latent period for radiation-induced cancer. In
dealing with the latent period, we adopted the method used in the study
of NRPB in the United Kingdom (20). Namely, 2 years for leukemia and10 years for other cancers were set as the minimum latent periods, andradiation doses were summed from the beginning of radiation work up
to these numbers of years before the terminal date of the observation.
Thus some subjects might move from a certain dose class to a lower doseclass. Similarly, the first 2 years of follow-up for leukemia and 10 years
for other cancers, respectively, after first employment to radiation work
were excluded from the observation period. Accordingly, the numbers ofdeaths during these periods were also excluded from the analysis.
If the observed number of deaths was less than 30 and the estimatedtrend P value was lower than 0.10, the results were confirmed by thesimulation method (25). Furthermore, to avoid inflated detection of statistical significance during repeated multiple tests, supplementary multiple comparison analysis (Bonferroni’s method) was performed (26).

RESULTS

External Comparison
The total number of deaths was 5,527, including 2,138
cancer deaths, during the observation period 1986 through1997 in the total study population (Table 6). The SMR (andits 95% CI) for deaths due to all causes, non-neoplastic
diseases, and all cancers was 0.90 (0.87–0.92), 0.80 (0.77–0.84) and 0.94 (0.90–0.98), respectively. They were all significantly less than 1. The total number of deaths was 2,934,
including 1,191 cancer deaths in the prospective study population during the observation period 1991 through 1997
(Table 7). The SMR (and its 95% CI) for deaths due to allcauses, non-neoplastic diseases, and all cancers was 0.94
(0.90–0.97), 0.86 (0.82–0.91), and 0.98 (0.93–1.04), respectively. The former two were both significantly less than1, whereas that of all cancers was not significantly different
from 1. In addition, all of the SMRs for these causes ofdeath were lower in the total study population than in theprospective study population, probably due to a certain
amount of incomplete retrospective follow-up (see the Discussion). The SMR for site-specific cancers, including leukemias, was not significantly different from 1 in the prospective study population. Incidentally, no case among theleukemia was certified as chronic lymphocytic leukemia(CLL).

TABLE 5Distribution of the Final Residence Area of Study Subjects in the Prospective Study Population by the 8 Major
Districts in the Entire Country by Dose Group
Dose group (mSv)
District

,10

10–20

20–50

50–100

1001

A
B
C
D
E
F
G
H
Total

11,296 (13.6)b34,481 (41.4)
6,144 (7.4)
6,070 (7.3)
11,179 (13.4)
5,431 (6.5)
2,461 (3.0)
6,158 (7.4)
83,220 (100.0)

2,296 (18.5)
3,838 (30.9)
1,309 (10.5)
651 (5.2)
1,930 (15.5)
945 (7.6)
322 (2.6)
1,130 (9.1)
12,421 (100.0)

3,261 (24.7)
3,468 (26.3)
1,637 (12.4)
788 (6.0)
2,029 (15.4)
732 (5.5)278 (2.1)
1,004 (7.6)
13,197 (100.0)

2,039 (30.7)
1,504 (22.6)
890 (13.4)
384 (5.8)
1,055 (15.9)
256 (3.9)
88 (1.3)425 (6.4)
6,641 (100.0)

1,585 (39.6)
675 (16.9)
585 (14.6)
202 (5.0)603 (15.1)
109 (2.7)
33 (0.8)213 (5.3)
4,005 (100.0)aab

From north to south, A: Hokkaido and Tohoku, B: Kanto, C: Hokuriku, D: Chubu, E: Kinki, F: Chugoku, G: Sikoku, H: Kyusyu.
Percentage in parentheses.

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IWASAKI ET AL.

TABLE 6
SMR by Cause of Death during the Observation Period 1986–1997 in the Total Study Population

SMR

95% confidence
interval

P value fortwo-sided
test

6,168.8902.7
2,933.8
2,332.3

0.90
1.06
0.80
0.94

(0.87–0.92)(0.99–1.13)(0.77–0.84)(0.90–0.98)

0
0.085
0
0.002

2,273.9
48.3
119.3
481.9
141.6
109.5
390.2
73.1
129.5
410.9
33.8
23.4
37.4
37.7
57.3
17.8
67.6
2,206.3

0.94
0.79
0.84
0.89
1.02
0.87
1.04
0.96
0.98
0.97
0.95
1.15
0.86
0.69
0.80
1.12
0.89
0.94

(0.90–0.98)(0.56–1.08)(0.68–1.02)(0.81–0.98)(0.86–1.20)(0.70–1.06)(0.94–1.14)(0.75–1.21)(0.82–1.17)(0.87–1.07)(0.65–1.34)(0.76–1.68)(0.58–1.21)(0.45–1.01)(0.59–1.07)(0.69–1.74)(0.68–1.14)(0.90–0.98)

0.005
0.159
0.085
0.015
0.875
0.180
0.471
0.765
0.860
0.510
0.818
0.525
0.421
0.067
0.153
0.685
0.390
0.007

Observednumber

Expected
numberAll causes
External causes
Non-neoplastic disease
All neoplasms

5,527
955
2,354
2,185

Malignant neoplasms
All sites
Oral, pharynx
Esophagus
StomachColon
RectumLiver
Gallbladder
Pancreas
Lung
Prostate
Bladder
Kidney and other and unspecified urinary organs
Brain and central nervous systema
Non-Hodgkin’s lymphoma
Multiple myeloma
LeukemiabAll sites except leukemia

2,138
38
100
428
144
95
405
70
127
397
32
27
32
26
46
20
60
2,078

Cause of deathab

Neoplasm of malignant, benign and unspecified nature.
Number of cases of chronic lymphocytic leukemia was zero.

Internal Comparison
The results of the internal comparison to be presented
will be limited to the prospective study population, because,
as will be discussed later, retrospective follow-up of thetotal study population suffered from selection bias. The result of the analysis without consideration of the latent period are shown in Table 8 and those including a correction
for the latent period for cancers are presented in Table 9.
The total number of deaths with cancer was 1,191 without
consideration of the latent period, but it was reduced to
1,076 with inclusion of the latency. The results of analyses
were almost comparable between these two groups.
Although the total mortality rate increased significantlywith increasing cumulative dose (P 5 0.017), it was mainly
ascribed to deaths due to external causes; the latter showeda clearly and significantly elevated mortality in higher compared to lower dose classes (P , 0.001), whereas nonneoplastic diseases showed no apparent trend of increase
with dose (P 5 0.371). For cancers of all sites, though the
O/E ratio exhibited a slight tendency of an increase fromthe lowest to the highest dose classes, the trend was notstatistically significant, either with (P 5 0.099) or without(P 5 0.280) consideration of the latent period. Even after
the exclusion of leukemia, the results remained almost thesame. For leukemia, too, no trend of an increase was found(P 5 0.503 with and P 5 0.538 without consideration of
the latent period).

For site-specific cancers, an increase in the mortality ratewith increasing dose was not apparent for most cancers
except for cancers of the esophagus (P , 0.001 and P 5
0.002), stomach (P 5 0.025 and P 5 0.012) and rectum(P 5 0.024 and P 5 0.071), and multiple myeloma (P 5
0.070 and P 5 0.047), where the two P values in parentheses are with and without consideration of the latent period, respectively. For multiple myeloma, P values wereobtained by the simulation method (24). When the multiple
comparison test (Bonferroni’s method) was applied to theresults for these cancers, the trends for cancer of the stomach (P 5 0.382 and P 5 0.242) and rectum (P 5 0.370
and P 5 0.816) and multiple myeloma (P 5 0.748 and P
5 0.670) were found to be non-significant, while a significant trend remained for cancer of the esophagus (P ,0.001 and P 5 0.045).
DISCUSSION

Results of the external comparison revealed that, for major causes of death, the calculated SMR values were generally lower in the total study population than in the prospective one. This may be due in part to the fact that theretrospective follow-up period covered more young andthus newly employed workers than the prospective one, sothat the healthy worker effect should be manifested morestrongly (27). However, it seems probable that the lower

233

MORTALITY OF NUCLEAR INDUSTRY WORKERS IN JAPANTABLE 7
SMR by Cause of Death during the Observation Period 1991–1997 in the Prospective Study Population

Observednumber

Expected
numberSMR

95% confidence
interval

P valuefor
two-sidedtest

All causes
External causes
Non-neoplastic diseases
All neoplasms

2,934
397
1,305
1,215

3,137.7382.7
1,513.7
1,241.2

0.94
1.04
0.86
0.98

(0.90–0.97)(0.94–1.14)(0.82–0.91)(0.92–1.04)

0
0.481
0
0.465

Malignant neoplasms
All sites
Oral, pharynx
Esophagus
StomachColon
RectumLiver
Gallbladder
Pancreas
Lung
Prostate
Bladder
Kidney and other and unspecified urinary organs
Brain and central nervous systema
Non-Hodgkin’s lymphoma
Multiple myeloma
LeukemiabAll sites except leukemia

1,191
24
63
230
63
49
232
46
67
238
21
14
20
12
22
8
28
1,163

1,212.6
26.7
65.0
245.0
77.3
58.5
206.1
40.1
69.9
230.3
21.6
13.4
20.6
17.6
29.5
10.1
30.9
1,181.7

0.98
0.90
0.97
0.94
0.81
0.84
1.13
1.15
0.96
1.03
0.97
1.04
0.97
0.68
0.74
0.79
0.90
0.98

(0.93–1.04)(0.58–1.34)(0.74–1.24)(0.82–1.07)(0.63–1.04)(0.62–1.11)(0.99–1.28)(0.84–1.53)(0.74–1.22)(0.91–1.17)(0.60–1.49)(0.57–1.75)(0.59–1.50)(0.35–1.19)(0.47–1.13)(0.34–1.57)(0.60–1.31)(0.93–1.04)

0.544
0.672
0.854
0.354
0.115
0.240
0.076
0.391
0.779
0.634
0.985
0.987
0.985
0.226
0.195
0.622
0.661
0.597

Cause of deathab

Neoplasm of malignant, benign and unspecified nature.
Number of cases of chronic lymphocytic leukemia was zero.

SMR in the total study population was caused mainly by
the fact that, at the start of the cohort study, more precise
information on residence address could be obtained forworkers who were alive and thus currently working compared to those who were deceased. Moreover, since currently employed workers were included more frequently inthe higher-dose group than in the lower-dose group, differential follow-up rates were introduced into the retrospective
study (data not shown). The prospective follow-up is lessaffected by this selection bias.
In the prospective study population, external comparisons showed a significantly lower total mortality rate thanJapanese males in general, possibly due to the healthy
worker effect (27). The total cancer mortality rate, forwhich the influence of this effect is considered to be small(28–30), was nearly the same as that of the general Japanese male population. For all site-specific cancers, including leukemia, the mortality rate was not significantly different from that of the general population.
The results of the internal comparisons did not demonstrate any significant trend of an increase in total cancer
mortality with radiation dose, either including or excluding
leukemia, both with and without consideration of the latent
period. No significant trend was found for an increase inleukemia mortality, whereas a significant trend was detected for certain gastrointestinal tract cancers and for multiple
myeloma. It should be emphasized that a statistically sig-

nificant result might be obtained by chance even when lowlevel radiation may not have a real health effect. Thus multiple comparison analysis was performed for the results ofinternal comparisons for individual site-specific cancers.
With this analysis a significant trend remained only for cancer of the esophagus.
The results of similar studies reported from other countries are quite variable with respect to cancer sites, with asignificant association of mortality with radiation dose being found for all sites (4, 7, 19), esophagus (12, 15), lung(4, 7, 19), skin (14), bladder (5), brain and central nervous
system (15), multiple myeloma (5, 6, 14, 16), leukemia (5,8, 10, 13, 14, 16). Although these results, including thoseof the present study, are associated with large variations, atleast the significant findings for cancer of the esophagus
and multiple myeloma, which are in agreement with thepresent study, deserve attention. For multiple myeloma,
however, special emphasis should not be placed on the present results because the observed number of cases was only
eight, six of which were in the less than 10 mSv dose class(Table 8). It should be noted that cancer of the pancreas,
which showed a positive trend in the first analysis (17),demonstrated no increase of mortality in the present analysis.
For cancer of the esophagus, on the other hand, the significant trend with dose observed in the present study isnotable because it was confirmed by multiple comparison

234

IWASAKI ET AL.

TABLE 8
Trend Analysis by Causes of Death during the Observation Period 1991–1997, after Adjustment for Age,Calendar Year and Residence Area, in the Prospective Study Population, without Consideration of the Latent
Periods for Cancersa
Cumulative dose group (mSv)
Causes of death
All causes
External causes
Non-neoplastic diseases
Malignant neoplasms
All sites
Oral, pharynx
Esophagus
StomachColon
RectumLiver
Gallbladder
Pancreas
Lung
Prostate
Bladder
Kidney and other urinary
Brain and CNSb
Non-Hodgkin’s lymphoma
Multiple myelomac
LeukemiadAll site except leukemia

,10

10–20

20–50

50–1001001

x2
P value2014
0.97(0.92–1.01)
236
0.88 (0.77–1.00)
914
0.98 (0.91–1.04)

320
1.10 (0.98–1.23)
46
1.08 (0.79–1.44)
142
1.11 (0.93–1.31)

349
1.13 (1.01–1.25)
56
1.21 (0.91–1.57)
150
1.11 (0.94–1.30)

138
0.91 (0.76–1.07)
31
1.28 (0.87–1.82)
57
0.88 (0.66–1.13)

113
1.20 (0.99–1.44)
28
1.86 (1.23–2.68)
42
1.04 (0.75–1.41)

2.122
0.017
4.372
0.000
0.328
0.371

835
0.98 (0.92–1.05)
18
1.05 (0.62–1.66)
38
0.83 (0.59–1.13)
146
0.90 (0.76–1.05)
48
1.02 (0.75–1.35)
32
0.93 (0.63–1.31)
164
0.99 (0.85–1.16)
39
1.18 (0.84–1.62)
46
0.97 (0.71–1.29)
172
1.00 (0.86–1.16)
18
1.14 (0.68–1.80)
13
1.36 (0.72–2.32)
120.86 (0.44–1.50)
11
1.39 (0.69–2.48)
17
1.09 (0.63–1.74)
6
1.00 (0.37–2.18)
19
0.99 (0.60–1.54)816
0.98 (0.91–1.05)

125
1.07 (0.89–1.28)
3
1.26 (0.26–3.69)
40.68 (0.18–1.73)
32
1.42 (0.97–2.00)
40.72 (0.20–1.85)
40.85 (0.23–2.18)
24
1.02 (0.65–1.52)
20.47 (0.06–1.69)
11
1.63 (0.82–2.92)30
1.30 (0.88–1.86)
00.00 (0.00–2.01)
00.00 (0.00–2.44)
20.98 (0.12–3.55)
00.00 (0.00–2.69)
1
0.46 (0.01–2.55)
00.00 (0.00–4.71)
20.72 (0.09–2.60)
123
1.08 (0.90–1.29)

138
1.11 (0.93–1.31)
3
1.20 (0.25–3.50)
81.32 (0.57–2.60)
28
1.15 (0.76–1.66)
6
1.01 (0.37–2.19)
7
1.34 (0.54–2.77)
29
1.19 (0.80–1.71)
40.84 (0.23–2.14)
40.56 (0.15–1.43)
26
1.06 (0.70–1.56)
00.00 (0.00–1.89)
10.58 (0.02–3.22)
41.82 (0.50–4.65)
10.66 (0.02–3.67)
31.30 (0.27–3.80)
00.00 (0.00–4.59)
5
1.57 (0.51–3.66)
133
1.10 (0.92–1.30)

50
0.82 (0.61–1.08)
00.00 (0.00–3.02)
10
3.28 (1.57–6.03)
100.82 (0.39–1.51)
4
1.44 (0.39–3.70)
20.73 (0.09–2.63)
8
0.68 (0.29–1.34)
00.00 (0.00–1.55)
4
1.11 (0.30–2.85)
50.43 (0.14–1.00)
1
1.07 (0.03–5.94)
00.00 (0.00–4.85)
2
1.85 (0.22–6.70)
00.00 (0.00–5.00)
00.00 (0.00–3.20)
1
3.63 (0.09–20.2)
1
0.58 (0.02–3.22)
49
0.83 (0.61–1.10)

43
1.14 (0.83–1.54)
00.00 (0.00–4.78)
3
1.51 (0.31–4.41)
14
1.81 (0.99–3.04)
10.61 (0.02–3.42)
4
2.18 (0.60–5.59)
7
0.95 (0.38–1.96)
10.62 (0.02–3.47)
20.95 (0.12–3.44)
50.72 (0.24–1.69)
2
3.99 (0.48–14.4)
00.00 (0.00–9.09)
00.00 (0.00–5.50)
00.00 (0.00–8.22)
1
1.36 (0.03–7.58)
1
4.22 (0.18–40.2)
10.93 (0.02–5.20)
42
1.15 (0.83–1.55)

0.584
0.280
21.228
0.890
2.891
0.002
2.253
0.012
20.136
0.554
1.469
0.071
20.3710.645
21.4960.933
20.1190.547
21.397
0.919
1.230
0.109
21.437
0.925
0.116
0.454
21.3850.917
20.239
0.595
—
0.047
20.095
0.538
0.608
0.271

Observed number of deaths are shown in the upper row, and O/E ratio (95% confidence interval) are shown in the lower row, respectively. In therightmost column, trend z value and P value in the upper row and lower rows, respectively.
b
Malignant, benign and unspecified neoplasms were included.
c
P value was estimated using the simulation method.
dNumber of cases of chronic lymphocytic leukemia was zero.
atests. However, examination of the O/E ratio for this cancer,
as seen in Table 8 for example, showed the difference tobe as large as about threefold between the lowest dose class(,10 mSv) and the two highest dose classes combined(501 mSv). This magnitude of difference could not be explained as being entirely due to the effect of radiation inview of recent risk estimates obtained from the study of A-

bomb survivors (31). This difference may have been causedby the influence of confounding factors, such as lifestyle,which were not taken into account in the present study.
One reason to suspect the association of confounding
factors with the positive trend observed for certain cancers
is the finding for external causes. At present, no explanation
can be offered for external causes of death, which showed

235

MORTALITY OF NUCLEAR INDUSTRY WORKERS IN JAPANTABLE 9Trend Analysis by Causes of Death during the Observation Period 1991–1997, after Adjustment for Age,Calendar Year and Residence, in the Prospective Study Population for Cancers with Latent Periods of 2 Yearsfor Leukemia and 10 Years for Solid Cancers, Assumed in the Analysisa
Cumulative dose group (mSv)
Causes of death
All sites
Oral, pharynx
Esophagus
StomachColon
RectumLiver
Gallbladder
Pancreas
Lung
Prostateb
Bladder
Kidney and other urinary
Brain and CNSb
Non-Hodgkin’s lymphoma
Multiple myelomac
LeukemiadAll site except leukemia

,10

10–20

20–50

50–1001001

x2
P value

770
0.97 (0.90–1.04)
17
1.06 (0.61–1.69)
28
0.75 (0.50–1.08)
136
0.89 (0.75–1.05)
47
1.03 (0.76–1.37)
29
0.88 (0.59–1.27)
149
0.98 (0.83–1.15)
38
1.18(0.84–1.62)
44
1.00 (0.73–1.34)
161
1.00 (0.85–1.16)
18
1.13 (0.67–1.79)
12
1.31 (0.68–2.29)
110.80 (0.40–1.43)
7
1.22 (0.49–2.52)
13
0.97 (0.52–1.67)
5
1.10 (0.36–2.56)
19
0.98 (0.59–1.53)754
0.97 (0.90–1.04)

115
1.09 (0.90–1.31)
20.92 (0.11–3.33)
6
1.27 (0.47–2.77)
28
1.36 (0.91–1.97)
30.56 (0.11–1.62)
30.68 (0.14–1.98)
21
1.00 (0.62–1.53)
30.70 (0.14–2.04)
8
1.34 (0.58–2.65)
25
1.21 (0.78–1.79)
00.00 (0.00–1.97)
00.00 (0.00–2.73)
4
2.04 (0.56–5.22)
1
1.09 (0.03–6.09)
1
0.58 (0.02–3.21)
00.00 (0.00–5.93)
20.72 (0.09–2.60)
112
1.09 (0.90–1.31)

124
1.14 (0.95–1.36)
3
1.34 (0.28–3.92)
5
1.06 (0.34–2.46)
26
1.23 (0.80-1.80)
7
1.26 (0.51–2.60)
7
1.49 (0.60–3.07)
25
1.19 (0.77–1.76)
20.43 (0.05–1.55)
6
0.95 (0.35–2.07)
25
1.16 (0.75–1.71)
00.00 (0.00–1.91)
10.65 (0.02–3.59)
4
1.99 (0.54-5.10)
00.00 (0.00–4.27)
3
1.68 (0.35–4.91)
00.00 (0.00–6.71)
5
1.58 (0.51–3.68)
121
1.14 (0.95–1.36)

42
0.89 (0.64–1.20)
00.00 (0.00–3.65)
8
3.77 (1.63–7.42)
13
1.41 (0.75–2.41)
20.85 (0.10–3.08)
41.88 (0.51–4.81)
60.67 (0.25–1.46)
00.00 (0.00–1.89)
10.37 (0.01–2.04)
30.32 (0.07–0.95)
22.21 (0.27–7.98)
00.00 (0.00–5.49)
00.00 (0.00–4.09)
00.00 (0.00–10.2)
1
1.26 (0.03–7.01)
00.00 (0.00–18.6)
1
0.58 (0.02–3.24)
41
0.89 (0.64–1.21)

25
1.27 (0.82–1.88)
00.00 (0.00–7.82)
3
3.21 (0.66–9.38)
51.30 (0.42–3.04)
1
1.05 (0.03–5.88)
2
2.10 (0.26–7.60)
61.73 (0.64–3.77)
1
1.05 (0.03–5.85)
10.97 (0.03–5.41)
30.75 (0.16–2.20)
12.62 (0.07–14.6)
00.00 (0.00–13.0)00.00 (0.00–9.99)
00.00 (0.00–28.9)
00.00 (0.00–10.9)
1
15.8 (0.40–87.9)
1
1.02 (0.03–5.67)
24
1.25 (0.80–1.87)

1.288
0.099
20.993
0.840
4.374
0.000
1.963
0.025
20.018
0.507
1.984
0.024
0.826
0.205
21.3850.917
20.5920.723
21.198
0.884
0.741
0.229
21.3350.909
20.2540.600
21.0620.856
20.058
0.523
—
0.070
20.009
0.503
1.197
0.116

Observed number of deaths are shown in the upper row, and O/E ratio (95% confidence interval) are shown in the lower row, respectively. In therightmost column, trend z value and P value in the upper row and lower rows, respectively.
b
Malignant, benign and unspecified neoplasms were included.
c
P value was estimated using the simulation method.
dNumber of cases for chronic lymphocytic leukemia was zero.
aa highly significant trend with radiation dose. Externalcauses consist mainly of suicide and accidents. Almost all
previous radiation epidemiology studies (4–11, 13–18, 20,21) have failed to show any increase in these causes ofdeath in relation to radiation exposure, except those of Ashmore et al. (19), who found a significant positive association of death from accidents with radiation exposure, andthose of Gilbert et al. (12), who found non-significant associations for external causes. They did not interpret thesefindings.
Since no causal relationship of radiation exposure, especially to such low doses as being considered in this study,
could be expected for external causes of death, the present

findings were probably influenced by some confounders.
Factors associated with these causes of death include thepersonality, lifestyle, occupation and socioeconomic statusof the individuals and the nature of the surrounding society,according to studies in other countries (32–35). Althoughepidemiological studies of these causes of death are limitedin Japan, the vital statistics collected by the government(36) showed that the mortality rate from external causes ofdeath is characterized by a great variability among different
industries.
The possible confounding factors must be taken into consideration since the effect of low-level radiation exposure
on cancer mortality is expected to be very small. Since the236

IWASAKI ET AL.

present study did not include information on such factors
as the lifestyle of the radiation workers, which might beconfounding the risk assessment, a questionnaire survey onlifestyle was subsequently performed separately in 1997
through 1999 (37). The subjects of that survey were 54,369
males and 470 females currently engaged in radiation work.
A self-administered questionnaire form was distributed
to and collected from the subjects by the management of
nuclear facilities. Valid answers were obtained from 48,281
male and 428 female subjects. Examination of whether thelifestyle differed among different dose groups was made by
the Mantel extension statistical test (38) only for the male
respondents, with cumulative radiation doses stratified into
five classes similarly to those used in this study. The results,
in relation to the cumulative radiation dose, could be summarized as follows.
1. A significantly larger percentage of tobacco smokers
was found with increasing dose. Furthermore, the number of cigarettes smoked per day was larger and the ageof commencement of tobacco smoking was younger inthe higher-dose groups.
2. Although the percentage of alcohol drinkers did not differ among the dose groups, those in the higher-dosegroups tended to be heavier alcohol drinkers and wereyounger when they began to drink.
3. Regarding the habit of drinking tea and suchlike, a lower
percentage of black tea drinkers was found with increasing cumulative dose.
4. Past history of occupational contact with certain specificharmful materials such as asbestos, organic solvents, etc.
was more frequent in the higher-dose groups.
5. Subjects in higher-dose groups underwent X-ray examinations of the upper digestive tract, as well as otherkinds of radiological examinations, less frequently.
These results indicated that, among these radiation workers, different dose groups had distinct characteristics intheir lifestyles. Though only about 18% (21,700) of theprospective study population examined in the present analysis was also included in that study, the proportion included
increased with increasing dose, up to 60% in the 1001 mSv
class. Thus it is felt that these results represent the situation
among members of the present study population fairly well,and the differences among them in lifestyle may have confounded the results of the present study, particularly withrespect to radiation dose.
For instance, tobacco smoking and alcohol drinking are
well known to influence the incidence of gastrointestinal
tract cancers, especially cancers of the esophagus (39). The
present finding regarding cancer of the esophagus may be
explained in part by this effect. The positive trend of stomach cancer mortality with increasing dose, which cannot beignored because of the large number of cases detected in
the present population, although the trend was not significant by multiple comparison analysis, could also have beenbrought about by some influence of confounding factors.

For stomach cancer, however, tobacco smoking and alcohol
drinking are not known to be strongly associated (40). Dietary factors such as salt-rich food as well as occupational
factors (41) should be taken into consideration for this. Furthermore, with respect to the increase in gastrointestinal
cancers in higher-dose groups, the last finding (5) in theabove-mentioned lifestyle study is especially noteworthy.
In Japan, population X-ray examinations of upper gastrointestinal tract cancers have been promoted from the 1970s
as a national health policy (42). The finding that those inhigher-dose classes received examinations less frequently
than those in lower-dose classes indicates that the former
workers tended to have less recognition of the need for theirown health care. Such lifestyle characteristics may increase
their mortality rate. At present, however, this is only speculation. The influence of confounding factors in the dose–
response relationship between radiation dose and mortality
must be examined in more detail.
The excess relative risk of cancer mortality per unit doseof radiation exposure (ERR/Sv) has been estimated in many
radiation epidemiology studies (4, 6–14, 16, 18–21). This
was not done in the present study because the influence ofconfounding factors was strongly suspected, especially forcertain solid cancers. On the other hand, there is no definite
evidence of an association of these lifestyle factors withleukemia according to present epidemiological knowledge(43). The only factor whose possible confounding influence
cannot be totally disregarded is occupational exposure tocertain leukemogenic chemical substances, as was suggested from the above-mentioned finding (4) from our questionnaire study (37). At present, no data are available on
the level of exposure to specific chemical substances amongindividual radiation workers. Another factor strongly associated with leukemia, especially in Japan, is infection byhuman T-cell leukemia virus (44). However, the main endemic area for this virus is Kyushu island. Only a verysmall proportion of the present study population resided inthis area (Table 5). Thus it seems unlikely that this factor
has influenced the present results.
An attempt to estimate the excess relative risk was madeonly for leukemia mortality by fitting the data to a linear
relative risk regression model (45) with the AMFIT program (46). The ERR/Sv estimates (90% CI) for leukemia
obtained in analyses without and with the correction for thelatent period were 20.42 (29.7, 8.9) and 0.01 (210.0,10.0), respectively. Because of the wide confidence interval, as was expected from the small numbers of observedcases (Tables 8 and 9), their quantitative evaluation is rather
limited. Still, it can be stated at least that the values arewithin the range (24.1–7.0) observed in other publishedstudies (8, 9, 11, 12, 16, 18–20), some of which (8, 11, 12,20) have estimated ERR only for leukemia other than CLL.
Furthermore, compared to the ERR estimate (4.62) fromthe study of the A-bomb survivors (31), the central estimateof the ERR/Sv in our study appears to be very small, eventhough the difference was not statistically significant.

MORTALITY OF NUCLEAR INDUSTRY WORKERS IN JAPANIn conclusion, the present results have not yielded any
definite evidence as to whether exposure to occupational
low-level radiation increases cancer mortality. The observation period in this study is short, and the average age ofthe subject population is rather young. Efforts are being
made to continue this study over a longer period and to
consider the possible effects of confounding factors to obtain more reliable information about the health effects of
low-dose and low-dose-rate radiation.
ACKNOWLEDGMENTS
We thank all members of the following committees for their collaboration in this study: the Study Evaluation Committee, the Study Operation
Committee, the Research Ethics Committee, and the Radiation Dosimetry
Committee, which were established under the aegis of the REA Board
Chairman to ensure that the study would be conducted properly. Thanks
are also due to all staff members of IRE and the Director of RADREC,
who provided personal dosimetry records.
Received: September 17, 2001; accepted: September 11, 2002

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