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 −1.2% in the all-cancer mortality ELR and mean difference of −6.4% in the mortality BLR. Whereas for incidence, the effect of adjusting by cancer-specific SMRs resulted in a mean change of −14.4% 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.

Health Impacts of Low-Dose Ionizing Radiation: Current Scientific Debates and Regulatory Issues

“…The HWE should be considered when a general population is selected as a reference to a population dealing with ionizing radiation in a workplace. 54 For example, employed people are generally healthier than the general population. Indeed, while the general population consists of either healthy individuals or unhealthy individuals, those persons from the general population who are not healthy are less likely to be employed.…”

Towards sustainable human space exploration—priorities for radiation research to quantify and mitigate radiation risks

“…The long latency periods, low statistics, and low doses preclude currently the assessment of the effect of the ISS missions of ~ half a year duration. Furthermore, a strong healthy worker effect 21 was observed in the NASA Longitudinal Study of Astronaut Health, masking possible radiation-induced cancer risks 22 . In fact, even if there is an apparent increase in melanoma and prostate cancer, this is likely to result from increased cancer screening.…”

Low-dose ionizing radiation increases the mortality risk of solid cancers in nuclear industry workers: A meta-analysis

“…There was no statistical significance of SMR for increasing total and solid cancer mortality risk in uranium facility workers when combined with nuclear power plant and medicinal research (49), and the health worker effect was observed. This effect consists of three components, namely the health worker survival (17)(18)(19), health worker exposure (52)(53)(54)(55) and health worker selection (55,56) effects in occupational exposure epidemiology, and leads to the selection of a working population that is healthier compared with the general population. As a result, the observed SMR of the cancers of interest in this study was lower compared with the control population.…”

“…The effect on health care workers was a source of bias in occupational epidemiological studies and was recorded (17)(18)(19). The risk was not statistically significant in terms of excess relative risk (ERR) and/or standard mortality ratio (SMR), but there was evidence of increasing cancer mortality risk from exposure to IR (20,21).…”