Sex differences in lung cancer incidence: a genetic model

Family histories pertaining to cancer of all anatomic sites were ascertained on 88 Caucasian patients (61 males, 27 females) with histologically verified lung cancer. Lifetable analysis revealed that relatives of female probands had a significantly higher risk for cancer (all sites) at younger age (p less than .04) compared to relatives of male probands. This trend was peculiar to nonsmoking-associated cancer sites, and was not apparent for smoking-associated cancer sites. We hypothesize that certain components of genetic liability to lung cancer are common to nonsmoking-associated malignant neoplasms, and that females who develop lung cancer are more extreme with respect to genotype than are males who develop lung cancer. Our hypothesis accounts for the lower incidence of lung cancer among females, as well as the apparent increased susceptibility to cancer among their relatives.