Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the Life Span Study of atomic bomb survivors.

Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed that unspecified bladder cancer had high radiation sensitivity with a notably high female-to-male excess relative risk (ERR) per radiation dose ratio and were the only sites for which the ERR did not decrease with attained age. These findings, however, did not consider lifestyle factors, which could potentially confound or modify the risk estimates. This study estimated the radiation risks of the most prevalent subtype of urinary tract cancer, urothelial carcinoma, while accounting for smoking, consumption of fruit, vegetables, alcohol and level of education (a surrogate for socioeconomic status). Eligible study subjects included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and had estimated radiation doses. Members were censored due to loss of follow-up, incident cancer of another type, death, or the end of calendar year 2001. Surveys (by mail or clinical interview) gathered lifestyle data periodically for 1963-1991. There were 63,827 participants in one or more survey. Five hundred seventy-three incident urothelial carcinoma cases occurred, of which 364 occurred after lifestyle information was available. Analyses were performed using Poisson regression methods. The excess relative risk per weighted gray unit (the gamma component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43-1.78) but the risks were not dependent upon age at exposure or attained age. Lifestyle factors other than smoking were not associated with urothelial carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00 compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to 3.4) were greatly changed after accounting for all lifestyle factors. A multiplicative model of gender-specific radiation and smoking effects was the most revealing though there was no evidence of significant departures from either the additive or multiplicative joint effect models. Among the LSS cohort members with doses greater than 0.005 Gy(w) (average dose 0.21 Gy(w)), the attributable fraction of urothelial carcinoma due to radiation was 7.1% in males and 19.7% in females. Among current smokers, the attributable fraction of urothelial carcinoma due to smoking was 61% in males and 52% in females. Relative risk estimates of smoking risk were approximately two for smokers compared to nonsmokers. After adjustment for lifestyle factors, gender-specific radiation risks and the F:M ERR/Gy(w), the ratios of excess urothelial carcinoma risk were similar to the estimates without adjusting for lifestyle factors. Smoking was the primary factor responsible for excess urothelial carcinoma in this cohort. These findings led us to conclude that the radiation risk estimates of urothelial carcinoma do not appear to be strongly confounded or modified by smoking, consumption of alcohol, fruits, or vegetables, or level of education.