Myeloperoxidase is a lysosomal enzyme found in high concentrations in human lung due to recruitment of neutrophils. Myeloperoxidase activates benzo[a]pyrene as well as aromatic amines in tobacco smoke and generates carcinogen-free radicals. A single base substitution (G to A) in the promoter region of the myeloperoxidase gene has recently been demonstrated to markedly reduce transcription. We developed an RFLP/PCR assay to test the hypothesis that the allele favoring lower transcription (A allele) reduces the risk of lung cancer. Among population controls, 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 70% reduced risk of lung cancer (odds ratio, 0.30; 95% confidence interval, 0.10–0.93; P = 0.04; 182 cases). A lesser reduction in risk was observed for African-Americans with this genotype (odds ratio, 0.61; 95% confidence interval, 0.26–1.41; 157 cases). Individuals who inherit two copies of an allele that reduces transcription of the myeloperoxidase gene may be at decreased risk of lung cancer.

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Data collection was funded by grants 1RT-140 and 3RT-0403 from the State of California Tobacco Related Disease Research Program (to S. J. L.). The analysis of the MPO genetic polymorphism was supported by the Division of Intramural Research, National Institute of Environmental Health Sciences. Case ascertainment was supported in part by the California Public Health Foundation, subcontract 050-F-8709, which is supported by the California Department of Health Services as part of its statewide cancer-reporting program mandated by Health and Safety Code Sections 210 and 211.3. The ideas and opinions expressed herein are those of the authors, and no endorsement by the State of California, Department of Health Services, or the California Public Health Foundation is intended or should be inferred. Case ascertainment was also supported in part by the Division of Cancer Prevention and Control, National Cancer Institute, NIH, Department of Health and Human Services, under the assigned contract number N01-CN-25403.

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