Gender differences in genetic susceptibility for lung cancer

In contrast to men, the incidence of lung cancer among women has increased over the past decade. The basis for this increase among female smokers rema ins unknown. Surgical patients with a diagnosis of lung cancer and control subjects without a history of malignancy completed a smoking questionnaire and donated a blood sample. DNA was extracted from peripheral mononuclear c ells and genotyped for polymorphisms in cytochrome P450 1A1 (CYP1A1) (exon 7) and glutathione S-transferase M1 (GSTM1) (null). No gender differences i n either age at diagnosis or histological subtype were observed among lung cancer patients. In both patients (n = 180) and controls (n = 163), females smoked significantly less than males. The pack-year history associated wit h adenocarcinoma was smaller than that for squamous cell carcinoma. No sign ificant association was observed between the GSTM1 null genotype and cancer risk. However, women had a larger cancer risk than men (odds ratio 4.98 vs . 1.37) if they possessed the mutant CYP1A1 genotype. Female cancer patient s were significantly more likely than female controls to have both the CYP1 A1 mutation and GSTM1 null genotype. The combined variant genotypes conferr ed an odds ratio of 6.54 for lung cancer in women versus 2.36 for men, inde pendent of age or smoking history. These data suggest that polymorphisms in CYP1A1 and GSTM1 contribute to the increased risk of females for lung canc er. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.