Mismatch Repair Gene Polymorphisms and Association with Lung Cancer Development

hMLH1 and hMSH2 are two of the main members of the mismatch repair (MMR) genes family. Polymorphism of MMR genes is associated with a risk of developing sporadic and hereditary tumors. In the present case-control study, we investigated the promoter polymorphisms of selected mismatch repair genes: hMLH1 (rs1800734) and hMSH2 (rs2303425), and the risk they present regarding the development of lung cancer in the Slovak population. The study included 422 lung cancer cases, 511 controls for hMLH1 gene and 486 controls for hMSH2 gene. Polymorphism was investigated by a PCR-RFLP method. The risk of cancer development was evaluated in both dominant and recessive genetic models. The evaluation of rs1800734 polymorphism in patients in the dominant model showed a significantly decreased risk of lung cancer in the presence of at least one variant allele A (genotype GA and AA) (OR = 1.40; 95 % CI = 1.08–1.82; p = 0.01). These findings were equally strong expressed in women (OR = 2.00; 95 % CI = 1.23–3.25; p = 0.006). The results for rs2303425 polymorphism revealed an increased risk of lung cancer for variant genotype CC (OR = 2.28; 95 % CI = 1.12–4.63; p = 0.024) in the recessive model. A combination of rs1800734 and rs2303425 polymorphisms was shown to be risky for genotype GGCC; OR = 3.08; 95 % CI = 1.09–8.72; p = 0.03. The risk appeared even greater in female gender; (OR = 11.56; 95 % CI = 1.33–100.36, 1.26–94.66; p = 0.005. We conclude that the genotype of mismatch repair genes underscores the risk of lung cancer development in the Slovak population.