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Keywords:

  • polymorphism;
  • hMLH1;
  • lung cancer;
  • genetic susceptibility

Abstract

Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the −93G[RIGHTWARDS ARROW]A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 −93G[RIGHTWARDS ARROW]A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 −93G[RIGHTWARDS ARROW]A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR = 2.02; 95% CI = 1.15–3.55; p = 0.014) and the combined GG and GA genotype (adjusted OR = 1.83; 95% CI = 1.24–2.71; p = 0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (≤ 39 pack-years; adjusted OR = 1.95; 95% CI = 1.03–3.66; p = 0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR = 1.47; 95% CI = 0.82–2.61). These results suggest that the hMLH1 −93G[RIGHTWARDS ARROW]A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung. © 2004 Wiley-Liss, Inc.