Taken together—the enrichment of germline CYP2A6 deletion in LUAD (predominantly female non-smokers), its absence in smoking-related LUSC, and the higher Whole-gene deletion of CYP2A6 frequency in East Asians—these observations motivate a testable hypothesis that germline disruption of CYP2A6 may modulate tobacco-related mutational processes in lung cancer. The gene discussed is CYP2A6; the disease is lung cancer.