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 used 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 nonsmokers 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 is best described by the generalized interaction model rather than a simple additive or multiplicative model.

Figure 1

Smoking-related excess relative risk (ERR) as a function of duration and intensity. Panel A. ERR for a 50 pack-year smoker versus smoking duration. The upper axis indicates the smoking intensity (packs per day) required to reach 50-pack-years for the duration indicated on the lower axis. The fitted risk for a model that is linear in pack years with a log-quadratic duration effect is indicated with the solid line. The fitted ERR for the pack-years-only model is indicated by the dashed line. The points are estimates of the risk in smoking duration categories. Panel B. Variation in the lung cancer ERR with smoking intensity (cigarettes per day) for fixed numbers of pack years.

Figure 2

Gender-specific smoking effects on the excess relative risk (Panel A) and absolute rate (Panel B) as a function of age. The darker curves are for men and the lighter ones for women. The solid curves illustrate the modeled lung cancer risks for a person who smokes 20 cigarettes (one pack) per day from age 20. The long-dashed lines indicate the risk for an individual who stopped smoking at age 50. The short-dashed lines in Panel B indicate the risk for non-smokers. The curves correspond to risk for an unexposed person born in 1915.

Figure 3

Effects of attained age (Panel A) and age at exposure (Panel B) on the excess relative risk (ERR) per Gy. The plots compare the gender-averaged risk estimates for three joint effect models. The generalized multiplicative model for non-smokers is indicated by the dark solid line while the additive model is indicated by the long-dashed line. For both of these models the ERR is relative to the risk for non-smokers. The short-dashed line is for a model with no adjustment for smoking. In this model the ERR is relative to the risk for an unexposed cohort member without regard to smoking status.

Figure 4

Variation of the excess relative risk (ERR) with smoking intensity. The gender-averaged risk estimates at age 70 following radiation exposure at age 30. Smoking was assumed to start at age 20 so that smoking duration was fixed at 50 years in this figure. Panel A describes the joint effect of radiation and smoking relative to the baseline rate for a non-exposed non-smoker. The thin long dashed line is the fitted ERR for a person with no radiation exposure. The solid line is the fitted ERR following exposure to 1 Gy under the generalized multiplicative model, the thick dashed line is the fitted risk under a simple multiplicative model, and the short-dashed line is the fitted ERR under a simple additive joint effect model. The points are based on a generalized multiplicative model in which smoking intensity categories replaced the linear-quadratic function of log intensity used in the generalized multiplicative model. Panel B presents radiation-associated excess risks for an exposure of 1 Gy relative to the risk of an unexposed person with the same smoking history.