Biologically Based Analysis of Lung Cancer Incidence in a Large Canadian Occupational Cohort with Low-Dose Ionizing Radiation Exposure, and Comparison with Japanese Atomic Bomb Survivors

Abstract

Lung cancer incidence is analyzed in a large Canadian National Dose Registry (CNDR) cohort with individual annual dosimetry for low-dose occupational exposure to gamma and tritium radiation using the two-stage clonal expansion model (TSCE) and extensions of the model with up to 10 initiation steps. Models with clonal expansion turned off provide very poor fits and are rejected. Characteristic and distinct temporal patterns of excess relative risk (ERR) are found for dose response affecting early, middle, or late stages of carcinogenesis, that is, initiation with one or more stages, clonal expansion, or malignant conversion. Both fixed lag and lag distributions are used to model time from first malignant cell to incidence. Background rates are adjusted for gender and birth cohort. Lacking individual smoking data, surrogate annual smoking doses based on U.S. annual per capita cigarette consumption appear to account for much of the birth cohort effect, leaving radiation dose response relatively unchanged. The mean cumulative exposure for males receiving nonzero cumulative doses of gamma and tritium radiation was 18.2 mSv. The males have a significant dose response with 33 out of a total of 322 lung cancer cases attributable to radiation. There were 78 incident lung cancer among females, (with mean cumulative exposure of 3.8 mSv among females with nonzero exposure). The dose response for females appears smaller than for males but does not differ significantly from zero or from the male dose response. Findings for males include significant dose-response relationships for promotion and malignant conversion, but not initiation, and a protraction effect (sometimes called an inverse-dose-rate effect, where risk increases with protraction of a given dose). The dose response predicted by our analysis appears consistent with the risk for lung cancer incidence in the Japanese atomic bomb survivors cohort, provided that proper adjustments are made for duration of exposure and differences in background rate parameters.

We acknowledge support from the Department of Energy (DOE) under grant DE-FG02-03ER63675, and from the Center for Disease Control (CDC) under grant R01 0H07864. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. RERF is a private foundation funded equally by the Japanese Ministry of Health and Welfare and the U.S. Department of Energy through the U.S. National Academy of Sciences. The conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies.

Notes

We acknowledge support from the Department of Energy (DOE) under grant DE-FG02-03ER63675, and from the Center for Disease Control (CDC) under grant R01 0H07864. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. RERF is a private foundation funded equally by the Japanese Ministry of Health and Welfare and the U.S. Department of Energy through the U.S. National Academy of Sciences. The conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies.