A CASE-CONTROL STUDY OF CYTOCHROME-P4501A1, GLUTATHIONE-S-TRANSFERASE-M1, CIGARETTE-SMOKING AND LUNG-CANCER SUSCEPTIBILITY (MASSACHUSETTS, UNITED-STATES)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxificatio n of chemical carcinogens found in tobacco smoke; thus they may influe nce host susceptibility to lung cancer, In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mos tly White) we evaluated the association between the CYP1A1 MspI and GS TM1 polymorphisms and lung cancer risk, and their interaction with cig arette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant, The GSTM1 null genot ype was detected in 54 percent of cases and 52 percent of controls, Af ter adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a signifi cant increase in lung cancer risk, having both genetic traits was asso ciated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a subst antial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes, However, limitations of our stud y preclude a conclusion about this potential interaction.