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Myeloperoxidase (MPO) genotype and lung cancer histologic types: The MPO −463 A allele is associated with reduced risk for small cell lung cancer in smokers

MPO participates in the metabolic activation of tobacco carcinogens such as PAHs. A frequent MPO −463 G→A polymorphism in the promoter region reduces MPO transcription and has been correlated with >4‐fold lower benzo[a]pyrene–DNA adduct levels in the skin of coal tar–treated patients. Four of 7 case‐control studies found significantly reduced lung cancer risk associated with the A allele. Due to their different etiologies, we examined whether the MPO genotype affects histologic lung cancer types differentially. A case‐control study was conducted in 625 ever‐smoking lung cancer patients, including 228 adenocarcinomas, 224 SCCs, 135 SCLCs and 340 ever‐smoking hospital controls. MPO genotyping was performed by capillary PCR followed by fluorescence‐based melting curve analysis. Combining the MPO −463 (G/A+A/A) genotypes, a protective effect approaching significance (OR = 0.75, 95% CI 0.55–1.01) was observed when comparing all lung cancer cases to controls. Among histologic types of lung cancer, a weak protective effect was found for both adenocarcinoma (OR = 0.81, CI 0.55–1.19) and SCC (OR = 0.82, CI 0.56–1.21); a stronger and significant effect was found for SCLC (OR = 0.58, CI 0.36–0.95; p = 0.029). Our results also suggest that the MPO genotype varies among inflammatory nonmalignant lung diseases. In conclusion, our results emphasize the need for a separate analysis of lung cancer histologic types and an adjustment for inflammatory nonmalignant lung diseases in future MPO‐related studies. We confirm that the MPO −463 A variant affords a protective effect against lung cancer risk in smokers, which was strongest for SCLC patients. © 2002 Wiley‐Liss, Inc.