Lung cancer risk of Mayak workers: modelling of carcinogenesis and bystander effect

Lung cancer mortality in the period of 1948-2002 has been analysed for 6,293 male workers of the Mayak Production Association, for whose information on smoking, annual external doses and annual lung doses due to plutonium exposures was available. Individual likelihoods were maximized for the two-stage clonal expansion (TSCE) model of carcinogenesis and for an empirical risk model. Possible detrimental and protective bystander effects on mutation and malignant transformation rates were taken into account in the TSCE model. Criteria for non-nested models were used to evaluate the quality of fit. Data were found to be incompatible with the model including a detrimental bystander effect. The model with a protective bystander effect did not improve the quality of fit over models without a bystander effect. The preferred TSCE model was sub-multiplicative in the risks due to smoking and internal radiation, and more than additive. Smoking contributed 57% to the lung cancer deaths, the interaction of smoking and radiation 27%, radiation 10%, and others cause 6%. An assessment of the relative biological effectiveness of plutonium was consistent with the ICRP recommended value of 20. At age 60 years, the excess relative risk (ERR) per lung dose was 0.20 (95% CI: 0.13; 0.40) Sv(-1), while the excess absolute risk (EAR) per lung dose was 3.2 (2.0; 6.2) per 10(4) PY Sv. With increasing age attained the ERR decreased and the EAR increased. In contrast to the atomic bomb survivors, a significant elevated lung cancer risk was also found for age attained younger than 55 years. For cumulative lung doses below 5 Sv, the excess risk depended linearly on dose. The excess relative risk was significantly lower in the TSCE model for ages attained younger than 55 than that in the empirical model. This reflects a model uncertainty in the results, which is not expressed by the standard statistical uncertainty bands.