Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb sur vivors, women treated for cervical cancer, and patients irradiated for anky losing spondylitis. A total of 383 leukemias were observed among 283,139 st udy subjects. Considering all leukemias apart from chronic lymphocytic leuk emia, the optimal relative risk model had a dose response with a purely qua dratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term d id not improve the fit of the model. The relative risk decreased with incre asing time since exposure and increasing attained age, and there were signi ficant (P < 0.00001) differences in the parameters of the model between dat asets. These differences were related in part to the significant difference s (P = 0.003) between the models fitted to the three main radiogenic leukem ia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic my eloid leukemia). When the three datasets were considered together but the a nalysis was repeated separately for the three leukemia subtypes, for each s ubtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reducti ons of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indicati on of a difference between the studies in the relative risk and its distrib ution as a function of dose, age and time (P > 0.10 for all three subtypes) . The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by rando m variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequa te adjustment for cell sterilization effects, or errors in dosimetry could have played a role. (C) 1999 by Radiation Research Society.