Slováková P, Majerová L, Matáková T, Skereňová M, Kavcová E, Halašová E
Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 036 01, Martin, Slovak Republic,
Adv Exp Med Biol. 2015;833:15-22. doi: 10.1007/5584_2014_83.
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.
hMLH1和hMSH2是错配修复（MMR）基因家族的两个主要成员。MMR基因的多态性与散发性和遗传性肿瘤的发生风险相关。在本病例对照研究中，我们调查了所选错配修复基因hMLH1（rs1800734）和hMSH2（rs2303425）的启动子多态性，以及它们在斯洛伐克人群中与肺癌发生风险的关系。该研究纳入了422例肺癌病例、511例hMLH1基因对照和486例hMSH2基因对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法研究多态性。在显性和隐性遗传模型中评估癌症发生风险。在显性模型中，对患者rs1800734多态性的评估显示，至少存在一个变异等位基因A（基因型GA和AA）时，肺癌风险显著降低（OR=1.40；95%CI=1.08-1.82；p=0.01）。这些发现在女性中同样显著（OR=2.00；95%CI=1.23-3.25；p=0.006）。rs2303425多态性的结果显示，在隐性模型中，变异基因型CC患肺癌的风险增加（OR=2.28；95%CI=1.12-4.63；p=0.024）。rs1800734和rs2303425多态性的组合显示，基因型GGCC有风险；OR=3.08；95%CI=1.09-8.72；p=0.03。这种风险在女性中似乎更大；（OR=11.56；95%CI=1.33-100.36，1.26-94.66；p=0.005）。我们得出结论，错配修复基因的基因型强调了斯洛伐克人群中肺癌发生的风险。
