Radiation and Smoking Effects on Lung Cancer Incidence among Atomic Bomb Survivors

Abstract

While radiation increases the risk of lung cancer among members of the Life Span Study (LSS) cohort of atomic-bomb survivors, there are still important questions about the nature of its interaction with smoking, the predominant cause of lung cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were identified for the period 1958–1999. Individual smoking history information and the latest radiation dose estimates were utilized to investigate the joint effects of radiation and smoking on lung cancer rates using Poisson grouped survival regression methods. Relative to never-smokers lung cancer risks increased with the amount and duration of smoking, and decreased with time since quitting smoking at any level of radiation exposure. Models assuming generalized interactions of smoking and radiation fit markedly better than simple additive or multiplicative interaction models. The joint effect appeared to be super-multiplicative for light/moderate-smokers, with a rapid increase in excess risk with smoking intensity up to about 10 cigarettes per day, but additive or sub-additive for heavy-smokers smoking a pack or more per day, with little indication of any radiation-associated excess risk. The gender-averaged excess relative risk per Gy of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59 (95% confidence interval: 0.31–1.00) for non-smokers with a female:male ratio of 3.1. About one-third of the lung cancer cases in this cohort were estimated to be attributable to smoking while about 7% were associated with radiation. The joint effect of smoking and radiation on lung cancer in the LSS is dependent on smoking intensity, and best described by the generalized interaction model rather than a simple additive or multiplicative model.

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

“…43 Evidence from the LSS cohort also confirms that smoking significantly increases the excess risk of lung cancer. 111 …”

Effects of Radiation and Lifestyle Factors on Risks of Urothelial Carcinoma in the Life Span Study of Atomic Bomb Survivors

“…Weiss et al reported a relative risk of bladder cancer death of approximately 2 after exposure to an average of 2.2 Gy with no dependence on years since exposure; the study did not attempt to control for smoking (6). In studies of lung cancer incidence and smoking among the A-bomb survivors, Pierce et al (44) reported statistical evidence to reject an additive model, but not a multiplicative model, while Furukawa et al (15), using additional follow-up data, rejected both additive and multiplicative models in favor of a generalized interaction model in which multiplicative effects were observed among light smokers, but additive effects were observed among heavy smokers. Lung cancer, however, is more strongly associated with smoking than urothelial carcinoma and those studies had many more incident cases, which afforded greater power to detect interactions.…”

“…Concerns that smoking or other unaccounted for factors may confound or modify established bladder radiation risk estimates have been voiced in recent UNSCEAR and ICRP reports, and in the last LSS cancer incidence report (1,(12)(13)(14). Recently, evidence of ionizing radiation and smoking joint effects have been reported for lung cancer in the LSS, which further raises the possibility that lifestyle factors could modify bladder cancer risk estimates (15). The purpose of this study was to estimate the ionizing radiation risk of the most common subtype of bladder cancer (urothelial carcinoma) in the LSS cohort using the same methods as those used to derive the most recent ionizing radiation risk estimates, but with the inclusion of lifestyle factors to establish whether urothelial carcinoma radiation risk estimates were either confounded or modified by lifestyle factors.…”

Using Radiation Risk Models in Cancer Screening Simulations: Important Assumptions and Effects on Outcome Projections

“…In addition to the BEIR VII lung cancer model, a recent study has applied a pure ERR method to examine the effect of the interaction between smoking and radiation exposure (33). However, this analysis examined the lung cancer incidence among the Japanese atomic bomb survivors.…”