MYELOPEROXIDASE GENETIC-POLYMORPHISM AND LUNG-CANCER RISK

Myeloperoxidase is a lysosomal enzyme found in high concentrations in human lung due to recruitment of neutrophils. Myeloperoxidase activate s benzo[a]pyrene as well as aromatic amines in tobacco smoke and gener ates carcinogen-free radicals. A single base substitution (G to A) in the promoter region of the myeloperoxidase gene has recently been demo nstrated to markedly reduce transcription. We developed an RFLP/PCR as say to test the hypothesis that the allele favoring lower transcriptio n (A allele) reduces the risk of lung cancer, Among population control s, 7.8% of 459 Caucasians and 9.4% of 244 African-Americans inherited two copies of the A allele. Caucasians with the A/A genotype were at 7 0% reduced risk of lung cancer (odds ratio, 0.30; 95% confidence inter val, 0.10-0.93; P = 0.04; 182 cases), A lesser reduction in risk was o bserved for African-Americans with this genotype (odds ratio, 0.61; 95 % confidence interval, 026-1.41; 157 cases), Individuals who inherit t wo copies of an allele that reduces transcription of the myeloperoxida se gene may be at decreased risk of lung cancer.