-93G→A polymorphism of hMLH1 and risk of primary lung cancer

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→A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 -93G→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→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→A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.