Biologically-based risk estimation for radiation-induced chronic myeloid leukemia

Radiation cancer risks are typically determined by the use of simple statis tical descriptions of epidemiological data. It is important in risk assessm ent in general, however, to attempt to incorporate as much biological infor mation into the risk models as possible. We illustrate this by presenting a biologically-based linear-quadratic-exponential (LQE) incidence rate model for radiation-induced chronic myeloid leukemia (CML). The model consists o f a linear-quadratic dose-response for the induction of BCR-ABL, a waiting time distribution between BCR-ABL formation and detection of CML, and an ex ponential cell-killing term that multiplies both the background and induced incidence rates. Using data exclusive of the A-bomb survivor cohort, Bayes ian priors are defined for each of the nine parameters in this LQE model. T he priors are based on chromosomal translocations in lymphocytes, hematopoi etic stem cell survival experiments, CML waiting times in women irradiated for benign disease, the background CML incidence rate in the U.S. populatio n, and genomic DNA target sizes of BCR and ABL. Fixing three of the LQE mod el parameters to the means of their priors, maximum likelihood estimates of the remaining six parameters were obtained using A-bomb survivor incidence data for Hiroshima males. The likelihood estimates and the corresponding s ix prior distributions, both approximated as multivariate normal, were then used to form Bayesian posteriors for the six parameters not fixed. With th ese posteriors the LQE model yields Q gamma*=0.0042 Gy(-l) where Q gamma* i s the upper 95% confidence bound of the lifetime CML risk per person-gray i n the Limit of low doses of gamma-rays. This value is slightly less than Q gamma* =0.0049 Gy(-1) obtained from likelihood estimates of the LPE paramet ers, and substantially less than Q gamma*=0.0158 Gy(-l) obtained for a simp le statistical model linear in dose for kermas less than 4 Gy.