A model for radiation-related cancer suggested by atomic bomb survivor data

The age-time patterns of excess cancer risk among A-bomb survivors followed up by the Radiation Effects Research Foundation inevitably carry implications regarding the mechanisms of radiation-related cancer. It has recently been found, quite surprisingly and in contrast to impressions given by the relative risks, that for most solid cancers the excess incidence rates themselves depend very little on age at exposure or time since exposure, but mainly on attained age. This paper investigates a mechanistic model that conforms to these age-time patterns. The essence of the model, which is highly idealized, is that: (a) a cancer is caused by mutations that accumulate in a stem cell throughout life, essentially the Armitage-Doll multistage model, and (b) radiation is a general mutagen that can cause virtually any of these mutations. Although postulate (b) departs from previous modeling considerations, the extent to which it explains various aspects of the data in substantial detail is remarkable. A strength of the model is that, similarly to the Armitage-Doll multistage model but differently from many others, it predicts characteristic age-time patterns of excess rates rather independently of its parameter values. The consequence of (a) is that, in Armitage-Doll fashion, background rates increase throughout life as a power of age. The consequence of (b) is that excess absolute rates do not depend on age at exposure and increase with age to a power one less than that of the background rates. Thus the excess relative risk, which is the ratio of these rates, decreases throughout life as 1/age with no dependence on age at exposure. Although this age pattern of relative risks corresponds closely to the RERF data for solid cancer, the interpretation of such a description is quite different from the usual one in which age at exposure plays a primary role. (C) 1999 by Radiation Research Society.