Journal of Molecular and GeneticMedicine

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ISSN: 1747-0862

ResearchArticle
Research Article

Kudo et al., J Mol Genet Med 2017, 11:3
DOI: 10.4172/1747-0862.1000275

Open Access

The Adjustment Effects of Confounding Factors on Radiation Risk
Estimates: Findings from A Japanese Epidemiological Study on Low-DoseRadiation Effects (J-EPISODE)
Kudo S*, Ishida J, Yoshimoto K, Ohshima S, Furuta H and Kasagi F

Institute of Radiation Epidemiology, Radiation Effects Association, 1-9-16 Kajicho, Chiyoda-ku, Tokyo, 101-0044, Japan

Abstract
Purpose: To investigate the degree of any decreasing effects for excess relative risk (ERR) of radiation exposure
caused by adjusting for smoking and years of education.
Methods: In this cohort study, we assembled a cohort of 41,742 males who responded to a lifestyle questionnaire
survey performed in 2003, were registered in the Radiation Dose Registry as Japanese nuclear workers by the endof March 1999. There were a total of 215,000 person-years, while the number of deaths for all cancers excluding
leukemia was 978. Poisson regression was used to quantify ERR per Sv and a comparison of ERRs was performed
before adjustment for smoking or years of education and after those adjustments.
Findings: For all cancers excluding leukemia, the ERR/Sv was 0.78 (90%CI: -0.65, 2.20). However, it decreased
to 0.31 (-1.03, 1.65) when adjusted for smoking and to 0.42 (-0.94, 1.79) when adjusted for years of education. Whenadjusting for both smoking and years of education, it decreased to 0.08 (-1.22, 1.39).
Conclusion: Our results demonstrate the importance of collecting lifestyle data and adjusting for them whenestimating radiation risk.

Keywords: Radiation epidemiology; Confounding factor; Cancer;
Smoking-related cancer
Introduction
Current radiation protection standards are based upon therecommendations of the International Commission on RadiologicalProtection (ICRP). The dose limits of the ICRP are mainly based on
the results of the studies of atomic bomb survivors who were acutely
exposed to high-dose rate radiation. However, the causal relationshipbetween low-dose rate radiation and health effects remains unclear
despite a number of epidemiological studies undertaken to obtain
scientific evidence on the health effects of low-dose and low-dose
rate of radiation exposure among radiation workers. One reason isthat the estimate of radiation risk is likely to be biased or distorted by
confounding factors, such as smoking which are known as one of majorrisk factors that affect mortality. However, very few published studies
have adjusted for smoking.
The Institute of Radiation Epidemiology (IRE) of the Radiation
Effects Association (REA) initiated an epidemiological study of Japanese
nuclear workers in 1990 (J-EPISODE: Japanese epidemiological study
on low-dose radiation effects). The follow-up population consists ofnuclear workers of Japanese nationality who were registered with theRadiation Dose Registration Center (RADREC) of the REA as of theend of March 1999. A lifestyle questionnaire survey completed by a partof the follow-up population provided information about lifestyle andsocio-economic status. We used this information to quantify the effectsof these factors on the radiation risk estimate.

Materials and Methods
The follow-up population consisted of workers of Japanesenationality from all nuclear power plants, research institutes, and fuelprocessing companies registered in the Radiation Dose Registration
Center (RADREC) as of the end of March 1999. We confirmed vital
status by requesting copies of the residence registration cards (RRCs) ofeach subject from their municipalities. The RRCs were issued when theJ Mol Genet Med, an open access journal
ISSN: 1747-0862

subjects were alive, and deleted RRCs were issued when subjects had
deceased or moved. The causes of death were obtained for those whosedeaths could be ascertained through the RRCs by linking the records
with death records approved for use and provided by the Ministry ofHealth, Labor, and Welfare, Japan. Indices used for record linkage weredate of birth, date of death, sex, and municipality code of residence[1]. The dose records supplied by RADREC to the IRE reported eachindividual’s amount of radiation exposure according to fiscal year.
Doses below detectable levels were rated as 0 mSv in the present study.
Dose data were available for this study for the entire period from 1957
to 2010 and were used to calculate the cumulative radiation dose forindividual workers. Personal dose equivalent Hp (10) values were usedin the analysis.
The lifestyle questionnaire was distributed by mail to nuclear facility
workers who were 40 years old or more on July 1, 2003. Based on thecumulative dose as of March 31, 2002, all workers exposed to 10 mSv or
more were surveyed, while 40 percent of workers with less than 10 mSv
exposure were sampled. The questionnaire was self-administered andincluded questions about smoking, years of education, etc. Of those
who replied, 41,742 male workers were assembled as a cohort. Female
workers were also followed up but were not included in the analysis
because they were too few in number.

*Corresponding authors: Mr. Shin’ichi Kudo, Institute of Radiation Epidemiology,
Radiation Effects Association, 1-9-16 Kajicho, Chiyoda-ku, Tokyo, 101-0044,
Japan, Tel: 813-5295-1493, Fax: 813-5295-1485; E-mail: s_kudo@rea.or.jp
Received June 21, 2017; Accepted July 18, 2017; Published July 21, 2017
Citation: Kudo S, Ishida J, Yoshimoto K, Ohshima S, Furuta H, et al. (2017) The
Adjustment Effects of Confounding Factors on Radiation Risk Estimates: Findings fromA Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE). JMol Genet Med 11: 275 doi:10.4172/1747-0862.1000275
Copyright: © 2017 Kudo S, et al . This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author andsource are credited

Volume 11 • Issue 3 • 1000275

Citation: Kudo S, Ishida J, Yoshimoto K, Ohshima S, Furuta H, et al. (2017) The Adjustment Effects of Confounding Factors on Radiation Risk Estimates:
Findings from A Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE). J Mol Genet Med 11: 275 doi:10.4172/17470862.1000275

Page 2 of 3
We used the person-years method for the death rate denominatorand observed deaths for the death rate numerator. The person-years
is obtained by summing the number of observed years for eachmember of the cohort. All individuals contributed person-years at risk,
excluding the first two years from the date of reply to the questionnaire[2], until the earliest of (a) the date of last known vital status, (b) thedate of death, or (c) December 31, 2010. Poisson regression models
were applied to analyze radiation risks based on the number of deaths
and the person years cross-classified by the attained age (20-, 25-, ...
100+), area of residence (divided into eight areas within Japan), timedependent radiation dose (<0.005, 0.005-, 0.01-, 0.02-, 0.05-, 0.1+Sv), smoking status (current, former, never, unknown), and years ofeducation (<10, 10-, 13+, unknown). No adjustment was made forcalendar period because the follow-up period was short (2005–2010).
Each stratum of the cross-classification included the number of deaths,
the number of person years, and the person-weighted mean values ofattained age, radiation dose. The model used to estimate radiation risks
was a linear excess relative risk (ERR) model:λλ0 (a, r)eα1z1+α 2z 2 (1 + β d)where λ is the death rate at dose, λ0 is the background death rate
(stratified by a: attained age and r: residence), d is the person-year
weighted cumulative dose in Sv, z1 represents the category of smoking
status and z2 represents the category of years of education in eachstratum. The parameters α1 and α2 represents the coefficient of z1 andz2, respectively. β is the ERR per Sv (ERR/Sv). ERR expressed as relativerisk (RR) minus one, is equal to a portion of the RR accounted for byradiation dose. We calculated 90% Wald-based confidence intervals.
The cross-tabulation and model fitting were performed using theEpicure statistical package [3]. We used this model to examine theconfounding effects of smoking and years of education by comparing
the ERRs of radiation risks with and without adjustment for smoking
and years of education. Cumulative doses were lagged by 10 years.

Results
Approximately 215,000 person-years were accumulated from 2005
to 2010 for 41,742 members of the cohort. The arithmetic mean andstandard deviation of age were 54.9 and 9.6 years respectively; themean cumulative dose was 25.6 mSv at the date on which responders
completed the questionnaire.
Regarding all cancers excluding leukemia, adjustment for onlyattained age and residence (hereafter “basic adjustment”) gave an
ERR of 0.78. This value decreased to 0.31 when adjusted for smoking.
Adjustment for years of education also decreased the ERR value
similarly to smoking, to 0.42, and this value further declined to 0.08
with adjustment for both smoking and years of education (Table 1).
Regarding for smoking-related cancer, basic adjustment gave an
ERR of 0.68. Adjustment for smoking showed a large decrease to 0.08,
whereas adjustment for years of education gave an ERR of 0.35, andadjustment for both smoking and years of education gave an ERR of-0.09 (Table 1).

Discussion
The reduction in ERR following adjustment for smoking was dueto the correlation with radiation [4]. The correlation of radiation dosewith smoking reflected the differences in smoking rates among job
status groups. For example, the group of workers who were engaged inmaintenance or repair of pressure vessels, pumps, etc. made up a higher
proportion of the high-dose group and also had higher smoking rates.
J Mol Genet Med, an open access journal
ISSN: 1747-0862

AdjustmentAll cancers excluding
leukemia (Obs=978)

Smoking-related
cancera (Obs=704)

ERR/Sv (90% CI)

ERR/Sv (90% CI)

Basicb

0.78 (-0.65, 2.20)

0.68 (-0.97, 2.33)

Basic+Smoking

0.31 (-1.03, 1.65)

0.08 (-1.44, 1.60)

Basic+Years of education

0.42 (-0.94, 1.79)

0.35 (-1.24, 1.94)

Basic+Smoking+Years ofeducation

0.08 (-1.22, 1.39)-0.09 (-1.58, 1.39)

Basic(Excluding lung cancer)

0.19 (-1.36, 1.74)-0.35 (-2.17, 1.46)

Buccal and pharynx, esophagus, stomach, liver, pancreas, nasal cavity, larynx,lung, bladder, kidney, ureter.
b
Adjusted only for attained age and residence.
aTable 1: The excess relative risk (ERR) for all cancers, excluding leukemia andsmoking-related cancer, in nuclear facility workers in Japan.

Sterling et al. have reported the following strong pattern in smoking
behavior: smoking is much more prevalent among occupationalgroups (and social strata) that also have greater exposure to hazards
in the workplace, whereas it is much less prevalent among groups lessexposed to these hazards [5]. The positive correlation between radiationdose and smoking shown in the present study might therefore reflect
the fact that blue-collar workers were more likely to smoke.
An indirect method that excluded lung cancer from all cancers hasoften been used as a surrogate for adjusting for smoking. However, theERRs obtained by excluding lung cancer from all cancers excluding
leukemia or smoking-related cancers were not similar to the ERRs
obtained by adjusting for smoking.
Adjustment for years of education also decreased the ERRs. This
reduction was caused by the correlation between radiation and yearsof education. This correlation possibly arose due to differences in thesocioeconomic status of workers in each dose category.

Conclusion
We demonstrated the effect of adjustment for a confounding factor
on the reduction of radiation risk estimates. Our results indicate theimportance of collecting lifestyle data and adjusting for them whenestimating radiation risk.
Funding
This work was fully funded by the Nuclear Regulation Authority. The funder had
no role in the study design, data analysis, data interpretation, or writing of the report.

Conflicts of Interest
The authors have no conflicts of interest.

Acknowledgements
This study protocol conformed to the Ethical Guidelines for Medical andHealth Research Involving Human Subjects of the Ministry of Health, Labor,and Welfare, Japan and the Ministry of Education, Culture, Sports, Science, andTechnology, Japan. The protocol was reviewed and approved by the Research
Ethics Committee of the REA.

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Citation: Kudo S, Ishida J, Yoshimoto K, Ohshima S, Furuta H, et al. (2017) The Adjustment Effects of Confounding Factors on Radiation Risk Estimates:
Findings from A Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE). J Mol Genet Med 11: 275 doi:10.4172/17470862.1000275

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J Mol Genet Med, an open access journal
ISSN: 1747-0862

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