Second Analysis of Mortalityof Nuclear Industry Workers in Japan
Motoi Murata, Sumio Ohshima, Shin-ichi Kudo, Takesumi Yoshimura,
Suminori Akiba, Toshiro Tango, Yasuhiko Yoshimoto, Yukiko Shimizu,
Tomotaka Sobue, Shizuyo Kusumi and Hiromichi Matsudaira
Radiation Effects Association, 1-9-16,Kajicho, Chiyodaku, 101-0044 Tokyo, Japan

Abstract
A cohort study of nuclear industry workers was begun in 1990 to determine the possible healtheffect of low dose radiation exposure. A follow-up study of about 244,000 male workers was conducted using
residence registration records. About 176,000 subjects were successfully followed up, and 5,527 deaths wereascertained during the period of observation 1986 through 1997. Underlying causes of death were identified
by record linkage with magnetic tape records of national vital statistics data. The standardized mortality ratio(SMR) was calculated with Japanese males in general as the reference population. Tests for trends in death
rates were made against cumulative radiation dose. The SMR (and its 95% confidence interval) was 0.90
(0.87-0.92) for all causes, 0.80 (0.77-0.84) for non-neoplastic diseases and 0.94 (0.90-0.98) for all cancer,
respectively. The lower SMR was ascribed to possible healthy worker effects, etc. In the trend analyses, thedeath rate for neither all cancers sites nor leukemia showed any positive correlation with radiation dose,
while significantly positive correlations were found for cancers of the esophagus (p<0.001), stomach(p<0.05) and rectum (p<0.05), and also for external causes (p<0.001). In lifestyle survey studies of 49,000
workers, both smoking and drinking habits were positively correlated with radiation dose. These lifestylecharacteristics may have been important factors affecting the present results.

Keywords: low level radiation, radiation effects, epidemiology, cancer

Introduction
A cohort study of nuclear industry workers was made with the aim to obtain scientific information
on health effect of exposure to low-level radiation in man. This study, the conduct of which had been
entrusted by the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), wasbegun in 1990 by the Institute of Radiation Epidemiology (IRE) of the Radiation Effects Association (REA)[1].

Materials and Methods
1) Follow-up Study
The study population consisted of approximately 244,000 radiation workers, who were registeredin the Radiation Dose Registration Center (RADREC) of REA as of the end of March 1995 and who satisfied
certain requirements such as having a record of exposure dose. First, personal identification information wasobtained from RADREC, including central registration number, name, gender and date of birth. Next, homeaddress information was acquired with the cooperation of nuclear facilities where the subjects worked. Then,the survival status of whether dead or alive was confirmed by obtaining residence registration certificatesfrom the local government offices of their residence. Excluded from the analysis were workers who could not
be located due to unknown address or because of expiration of the storage period (five years) for records that
had been removed from the residence register due to death or relocation. The follow-up involved both
retrospective and prospective observations.
For those whose death had been thus confirmed, the cause of death was ascertained by a record
linkage with magnetic tape copies (1986-1997) of vital statistic death records of the Japanese Ministry ofHealth, Labor and Welfare. Effective dose equivalent data registered at RADREC were used as the exposure
doses of the subject workers.
The "total study population" consisted of approximately 176,000 male workers identified througheither the retrospective or prospective follow-up. From this population, approximately 119,000 workers, who
had been prospectively followed-up, were designated as the "prospective study population". Female workers
were excluded from the study populations because of the small number of cases.

2) Statistical Analysis
The total period at risk was divided into three periods, 1986-1989, 1990-1994 and 1995-1997, andthe range of age of the subjects 20 to 85 years was stratified into 5-year age classes. In external comparisons,the standardized mortality ratio (SMR) and its 95% confidence interval (CI) were calculated.

In internal comparisons, trend analysis with score statistics was performed. Namely, the study
population was divided into five groups by cumulative dose levels of less than 10 mSv, 10-19 mSv, 20-49mSv, 50-99 mSv and 100 mSv or more, and the statistical significance was tested for whether the ratio ofobserved (O) to expected (E) numbers of deaths (O/E ratio) among cumulative dose-specific groups washigher at greater cumulative doses, by adjusting for the factor of regional differences (8 major districts ofJapan). The expected number of deaths in each dose group was calculated by assuming that the mortality rate
was the same as the age-specific and calendar-year-specific mortality rate of the study population. Analyses
were performed in two ways, either with or without consideration of the latent period to onset of cancer due
to radiation (two years for leukemia and ten years for other neoplasms). Furthermore, multiple comparison
analysis (Bonferroni's Method) was applied to prevent accidental judgment of "significant" during repeatedmultiple tests.

3) Lifestyle survey study
In addition to the main follow-up study, a supplementary questionnaire survey of lifestyle wasconducted for about 49,000 workers to examine whether any factor with known relationship to humancancers might play a role as a confounding factor in this follow-up study.
The subjects of this survey were those actually engaged in work at nuclear facilities during theperiod 1997-1999, when questionnaires were distributed and collected. The questionnaire was of aself-administered type and included questions on daily habits such as tobacco smoking, alcohol intake, tea
intake, etc., and also questions concerning occupational history of specific hazardous jobs and history ofmedical radiation exposures.
The responses were tabulated by age (<30, 30-, 40-, 50-, 60+ years) and radiation dose groups (<10,10-, 20-, 50-, 100+ mSv). Statistical tests were carried out to examine whether the percentage of positive
answers to each question showed any trend with increasing dose among the male respondents.

Results
1) Characteristics of the Subject Populations
The average period at risk for the 175,939 members of the total study population was 7.9 years.
The average individual cumulative dose was about 12 mSv and the total collective population dose was about
2,109 person-Sv. The mode of year of birth for the population was in the 1950s. There were 5,527 deaths, ofwhich 2,138 were due to cancers.
The average period at risk for the 119,484 subjects in the prospective study population was about
4.5 years. The average individual cumulative dose was about 15 mSv and the total collective population dosewas about 1,826 person-Sv. The mode of year of birth for the population was in the 1950s. There were 2,934
deaths, of which 1,191 were due to cancers.

2) External Comparison
When the latent period was not taken into consideration, the SMR (and 95% CI) for deaths due toall 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, in the total study population (Table 1), and was 0.94 (0.90-0.97), 0.86 (0.82-0.91),
and 0.98 (0.93-1.04), respectively, in the prospective study population. These values are significantly lessthan 1 except the SMR for all cancers in the prospective study population.
On the other hand, the SMR for site-specific cancers including leukemia was not significantly
different from 1 in either the total or prospective study population, irrespective of whether or not the latent
period was considered. The exception is gastric cancer (SMR=0.89) in the total study population when
examined without inclusion of the latent period,.

3) Internal Comparison
The results of internal comparisons (Table 2) presented below will focus on the prospective study
population, where bias due to failure of verification of death is considered to be less probable as was seen in
the results of external comparison. For neoplasms the results were limited to analyses that took the latent
period into consideration. The total number of deaths due to cancer was 1,191 without consideration of thelatent period, and this was reduced to 1,076 when the latent period was included.
Although the total mortality rate was increased significantly at higher cumulative doses, it wasmainly ascribable to deaths due to external causes (p<0.001). No significant trend was found for cancer in allsites (p=0.99). Nor was it seen for leukemia (p=0.503). The mortality rates for cancers of the esophagus(p<0.001), stomach (p=0.025) and rectum (p=0.024), and for multiple myeloma (p=0.07) showed asignificant or closely significant trend related to exposure dose, and a similar trend was found in analyses that
did not take the latent period into consideration. However, the trends for cancers of the stomach and rectum,and for multiple myeloma were not significant in tests by the multiple comparison method. No significant
trends were found for cancers other than these sites.

4) Questionnaire survey study
Statistical analyses of the results of the questionnaire survey on lifestyle revealed the following
characteristics for male workers at nuclear facilities in relation to the cumulative radiation dose.
a) The percentage of tobacco smokers was significantly increased at higher doses. Furthermore, the numberof cigarettes smoked per day was greater and the age of commencement of tobacco smoking was lower inthe higher dose groups.
b) Although the percentage of alcohol drinkers did not differ among dose groups, those with higher doses
tended to be heavier alcohol drinkers and younger at age when they started to drink.
c) Regarding the habit of drinking tea and suchlike, a lower percentage of black tea drinkers was observedwith increasing cumulative dose.
d) Those in higher dose groups showed higher rates of having participated in special health examination
programs and having been employed in hazardous work.
e) Respondents in higher dose groups tended to have not received gastrointestinal X-ray examinations orother kinds of radiological examinations.

Discussion
With focus on the results for the prospective study population, external comparisons showed asignificantly lower total mortality rate than among average Japanese males in general, seemingly due to thehealthy worker effect. The total cancer mortality rate, for which the influence of this effect is considered to besmall, was nearly the same as that of the average Japanese male population. All cancers including leukemia
showed no significant increase compared with the average Japanese male population.
Results of internal comparisons showed no significant trend either for cancer in all sites or forleukemia to increase with cumulative dose. Significant trends related to radiation dose were noted for somegastrointestinal tract cancers, especially esophagus cancer, but not for other cancers.
Other similar studies in various countries do not necessarily indicate a sufficiently significant
association with dose for all cancers or leukemia, but for various cancers of specific sites, to make therespective conclusions incompatible [2]. These reported results, including those of the present study, are at
great discrepancy, and, in many aspects, are not consistent with studies of atomic bomb survivors in
Hiroshima and Nagasaki. These differences seem to be caused partly by the fact that most of the studies do
not consider confounding factors such as lifestyle.
The questionnaire survey on lifestyle revealed that, in comparison with workers with lower
cumulative doses, those with higher cumulative doses smoked more, drank more, worked longer hours inspecific harmful operations, and participated less in gastrointestinal X-ray mass examinations. These
differences in lifestyle are predicted as having confounded the results of the present study. For instance,smoking and drinking are well known to strongly influence gastrointestinal tract cancers, including
esophageal cancer [3], and it is highly probable that the relationship of these cancers with cumulative dose
described above had been brought about by the effect of these confounding factors.
In this context, it is very probable that certain presently unrecognized confounding factors similarlymay have had influence on external causes of death, since no biomedically plausible explanation could begiven for a causative effect of radiation on such conditions.
It should also be noted that the actual period of observation in this study is still short and that theaverage age of the subject population was rather young.
When these points are taken into consideration, it does not seem that any conclusive evidence wasobtained from the present results as to whether low-level radiation doses increase cancer mortality. To obtain
more reliable scientific information on the health effects of radiation, it will be necessary to continue this kindof study over a long period, and to develop plans for the study of the effect of confounding factors.

References[1] Hosoda, Y., et al. First analysis of mortality of nuclear industry workers in Japan, 1986-1992. J. Health
Physics 32: 173-184, 1997
[2] UNSCEAR2000 Report Sources and Effects of Ionizing Radiation. Annex E. Occupational radiation
exposures. pp.497-654, 2000
[3] Kabat, G.C., et al. Tobacco, alcohol intake, and diet in relation to adenocarcinoma of the esophagus andgastric cardia. Cancer Causes Control 4: 123-134, 1993.

Table 1 SMRs by Cause of Death in Total Study Population (Latent Period: 0 year).
Cause of Death

Observed
Number

Expected
NumberSMR

95%
ConfidenceIntervalp Value forTwo-sided
TestAll Causes

5,527

6,168.8

0.90(0.87-0.92)

0.000

All Causes(excl. unknown or external causes)

4,539

5,266.1

0.86(0.84-0.89)

0.000

External Causes

955902.71.06(0.99-1.13)

0.085

Non-Neoplasticdiseases
All Neoplastic Diseases

2,354

2,933.8

0.80(0.77-0.84)

0.000

2,185

2,332.3

0.94(0.90-0.98)

0.002

All Malignant Neoplasms

2,138

2,273.9

0.94(0.90-0.98)

0.005

Oral, Pharynx

38

48.3

0.79

(0.56-1.08)

0.159

Esophagus

100

119.3

0.84

(0.68-1.02)

0.085

Stomach

428

481.9

0.89

(0.81-0.98)

0.015

Colon

144

141.6

1.02

(0.86-1.20)

0.875

Rectum

95

109.5

0.87

(0.70-1.06)

0.180

Liver

405

390.2

1.04

(0.94-1.14)

0.471

Gallbladder

70

73.1

0.96

(0.75-1.21)

0.765

Pancreas

127

129.5

0.98

(0.82-1.17)

0.860

Lung

397

410.9

0.97

(0.87-1.07)

0.510

Prostate

32

33.8

0.95

(0.65-1.34)

0.818

Bladder

27

23.4

1.15

(0.76-1.68)

0.525

Kidney and Other andUnspecified Urinary Organs
Brain and Central Nervous
System (a)

32

37.4

0.86

(0.58-1.21)

0.421

26

37.7

0.69

(0.45-1.01)

0.067

Leukemia (b)

60

67.6

0.89

(0.68-1.14)

0.390

Non-Hodgkin’s lymphoma

46

57.3

0.80

(0.59-1.07)

0.153

Multiple Myeloma

20

17.8

1.12(0.69-1.74)

0.685

0.94

(0.90-0.98)

0.007[By Site]

All Malignant Neoplasm
2,078
2,206.3
except Leukemia(a) Neoplasm of malignant, benign and unspecified.
(b) Number of cases for chronic lymphatic leukemia was zero.

Table 2 Trend Analysis by Cause of Death in Prospective Study Population with Latent Periods for Cancers.
Cause of Death<1010~

Cumulative Dose Group (mSv)
20~
50~

100+

p-Value forOne-sided
TrendAll Causes

2014 (a)2085.7

320
291.5

349
310.1

138
152.4

11394.2

0.017

All Causes(excl.unknownor external causes)
External Causes

1767
1805.4

269
247.0

292
261.8

107
127.2

85
78.5

0.296

236
268.6

4642.7

56
46.4

31
24.2

28
15.1

0.000

Non-Neoplasic
diseases

914
936.6

142
128.0

150
135.1

57
65.1

42
40.2

0.371

All Neoplastic
diseases

785
810.1

118
107.5

126
110.6

4247.9

25
19.9

0.119

All Malig.Neopl.

770
795.1

115
105.4

124
108.7

4247.2

25
19.6

0.099

17
16.1

22.2

3
2.2

0
1.0

00.5

0.840

Esophagus

28
37.5

64.754.7

8
2.1

3
0.9

0.000

Stomach

136
153.2

28
20.6

26
21.2

13
9.2

5
3.8

0.025

Colon

47
45.8

3
5.4

7
5.5

2
2.3

10.9

0.507

Rectum

29
32.8

3
4.4

7
4.7

4
2.1

2
1.0

0.024

Liver

149
152.5

21
21.0

25
21.0

6
9.0

6
3.5

0.205

Gallbladder

38
32.1

3
4.3

2
4.7

0
2.0

1
1.0

0.917

Pancreas

44
44.0

8
6.0

6
6.3

1
2.7

1
1.0

0.723

Lung

161
161.4

25
20.7

25
21.7

3
9.3

3
4.00.884

Prostate

18
15.9

0
1.90
1.9

20.910.4

0.229

Bladder

12
9.1

01.4

11.6

00.7

00.3

0.909

Kidney &Other Urinary

1113.8

4
2.04
2.0

00.9

00.40.600

Brain &(b)C.N.
System

7
5.7

1
0.9

00.9

0
0.4

0
0.1

0.856

(c)

1919.3

2
2.8

5
3.2

1
1.7

1
1.0

0.503

1313.3

11.7

3
1.8

1
0.8

00.3

0.523

5
4.6

0
0.6

0
0.6

00.2

1
0.1

0.070

24
19.1

0.116

[By Site]
Oral, Pharynx

Leukemia

Non-Hodgkin’s
Lymphoma
Multiple Myeloma

All Malig. Neopl.
754112
121
41
Except Leukemia
777.7
103.0
106.1
46.0
(a) Observed and expected numbers of deaths in the upper and lower parts, respectively.
(b) Malignant, benign and unspecified neoplasms were included.
(c) Number of cases for chronic lymphatic leukemia was zero.