Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors

Abstract

While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses.

Fig. 1

Age- and gender-specific absolute rate (upper panel) and excess relative risk of smoking (lower panel). Solid curves are for smokers who started at age 20 and never stopped. [The dotted curves are for past smokers who started at age 20 and stopped at age 50. The dashed curves are for lifetime never-smokers. The curves correspond to risk for an unexposed person born in 1915.

Fig. 2

Excess relative risk at 1 Gy as a function of smoking intensity, relative to unexposed smokers with the same smoking history (upper panel) and to unexposed non-smokers (lower panel). The curves correspond to risk at age 70, for one exposed at age 30 who smoked a pack/day for 50 years since age 20. In the upper panel, gender-averaged risks were plotted for each fitted interaction model. In the lower panel, the gender-averaged and gender-specific risks were plotted for the generalized multiplicative model. All points are categorical estimates of the ERRs (with 95% confidence intervals in the upper panel) based on a generalized multiplicative model in which smoking intensity categories replaced the linear-quadratic function of log intensity.