title: Adjustment of lifetime risks of space radiation-induced cancer by the healthy worker effect and cancer misclassification.
abstract: Background. The healthy worker effect (HWE) is a source of bias in occupational studies of mortality among workers caused by use of comparative disease rates based on public data, which include mortality of unhealthy members of the public who are screened out of the workplace. For the US astronaut corp, the HWE is assumed to be strong due to the rigorous medical selection and surveillance. This investigation focused on the effect of correcting for HWE on projected lifetime risk estimates for radiation-induced cancer mortality and incidence. Methods. We performed radiation-induced cancer risk assessment using Poisson regression of cancer mortality and incidence rates among Hiroshima and Nagasaki atomic bomb survivors. Regression coefficients were used for generating risk coefficients for the excess absolute, transfer, and excess relative models. Excess lifetime risks (ELR) for radiation exposure and baseline lifetime risks (BLR) were adjusted for the HWE using standardized mortality ratios (SMR) for aviators and nuclear workers who were occupationally exposed to ionizing radiation. We also adjusted lifetime risks by cancer mortality misclassification among atomic bomb survivors. Results. For all cancers combined ("Nonleukemia"), the effect of adjusting the all-cause hazard rate by the simulated quantiles of the all-cause SMR resulted in a mean difference (not percent difference) in ELR of 0.65% and mean difference of 4% for mortality BLR, and mean change of 6.2% in BLR for incidence. The effect of adjusting the excess (radiation-induced) cancer rate or baseline cancer hazard rate by simulated quantiles of cancer-specific SMRs resulted in a mean difference of [Formula: see text] in the all-cancer mortality ELR and mean difference of [Formula: see text] in the mortality BLR. Whereas for incidence, the effect of adjusting by cancer-specific SMRs resulted in a mean change of [Formula: see text] for the all-cancer BLR. Only cancer mortality risks were adjusted by simulated quantiles for misclassification, and results indicate a mean change of 1.1% for all-cancer mortality ELR, while the mean change in the all-cancer PC was approximately 4% for males and 6% for females. Conclusions. The typical life table approach for projecting lifetime risk of radiation-induced cancer mortality and incidence for astronauts and radiation workers can be improved by adjusting for HWE while simulating the uncertainty of input rates, input excess risk coefficients, and bias correction factors during multiple Monte Carlo realizations of the life table.
authors.affiliation: Center for Biostatistics, Houston Methodist Research Institute, 6565 Fannin Street, Suite MGJ6-031, Houston, TX 77030, United States.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Peterson
authors.affiliation: Center for Biostatistics, Houston Methodist Research Institute, 6565 Fannin Street, Suite MGJ6-031, Houston, TX 77030, United States.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kovyrshina
keywords: Epidemiology of cancer; Mathematical simulation; Radiation biology