Can passive smoking explain the higher radiation-related excess relative risk of lung cancer for women compared to men among atomic bomb survivors

Analyses of the Life Span Study (LSS) cohort of atomic bomb survivors have shown a sex difference in the incidence of lung cancer in relation to radiation exposure. Specifically, the excess relative risk (ERR) of lung cancer associated with radiation exposure is observed to be higher in women compared to men (the ERR/Gy for females = 1.32; the ERR/Gy for males = 0.34, F:M ratio = 3.91). The basis for this observed difference in ERR is unclear. One possibility is inadequate adjustment for passive smoking exposure in LSS participants. High rates of smoking among men, but not women, in the LSS suggest that non-smoking women in this population could have substantial passive exposure to tobacco smoke. Passive smoke exposure is a known risk factor for lung cancer, but was not measured for study participants. In our analysis, we simulated passive smoking by attributing smoking pack-years to nonsmoking women at various intensities based on male smoking patterns in the cohort. This yielded an increase in the radiation-related ERR/Gy estimates, leading to a higher F:M ratio, and a reduced smoking-related ERR estimate in women. Ultimately, the radiation-associated risks for lung cancer in women did not decrease as we had hypothesized, and our method of simulating passive smoke for women did not attenuate the F:M ratio towards one. However, given the exploratory nature of our simulation and limitations of the data, our results cannot rule out the possibility that passive smoke contributes to the higher radiation risk estimates for women compared to men in the LSS.