Investigating Temporal Patterns of Exposure Effects Using Multistage Models

Abstract

TAB1-O-05 Introduction: In environmental and occupational settings, carcinogenic exposures are often repeated or protracted over time. The time pattern of exposure accrual may influence subsequent temporal patterns of cancer risk. The approach of exposure-time window analysis is contrasted with direct fitting of multistage cancer models in order to evaluate temporal patterns of radiation-cancer associations. Methods: A cohort of over 18,000 nuclear workers hired at the Hanford Site between 1944 and 1978 was followed through 1994 to ascertain vital status and causes of death. External radiation dose estimates were derived from personal dosimeters. Associations between ionizing radiation and mortality due to lung cancer were quantified using exposure time windows and a multistage cancer model. Results: Time-window analyses suggest that the association between cumulative dose and lung cancer mortality are primarily due to doses accrued at ages 55+ (ERR/Sv = 9.05; 90% CI, 2.96–17.92). Direct fitting of a multistage model suggests that the best fit is obtained by assuming that the occupational exposure acts at the penultimate stage of a process with 7, 8, or 9 stages. Conclusions: Multistage models offer a way to jointly evaluate age-at-exposure and time-since-exposure in a constrained fashion. The results suggest temporal patterns that are quite different from the patterns presumed under the current compensation program for U.S. nuclear weapons workers and veterans exposed to ionizing radiation.