Temporal analysis of a dose-response relationship: leukemia mortality in atomic bomb survivors

A data analysis that incorporates time dependencies is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data on leukemia mortality--up to the end of 1978--are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-dependent L (linear in gamma dose)-Q (quadratic in gamma dose)-L (linear in neutron dose), L-L, and Q-L dose-response models are significantly improved (P less than 0.001) by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time (P = 0.002) and the current definition of RBE as a time-independent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit (P = 0.01) to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period (P greater than 0.30).