The Study Of HMLH1,hMSH2 Polymorphisms And Risk Of Gastric Cancer

Objective:Population-based case-control study on molecular epidemiology was carried out in Yixing city, which in the Jiangsu Province of China. To assess the association between the mismatch repair genes hMLH1 and hMSH2 polymorphisms and the risk of gastric cancer in China, four polymorphic sites with functional significance of hMLH1 and hMSH2 genes were selected. In the end the mechanism of the molecular genetics which lead to the incidence of gastric cancer will be clarified. Furthermore, this study will guide the prevention and therapy for high-risk groups.Methods:554 patients with gastric cancer cases and 592 cancer-free controls frequency-matched by age (±5) and sex were recruited in the study. The genotypes of the hMLH1-93G>A, I219V and hMSH2-118T>C, IVS12-6T>C polymorphisms were detected by TaqMan MGB probe method. Chi-square test was used to evaluate differences in frequency distributions of age, sex, smoking status and alcohol use between the cases and controls and further to assess the association with the occurrence of gastric cancer. Unconditional logistic regression was used to assess the association between each polymorphism and gastric cancer. We further analyzed the interaction of age, sex, smoking, alcohol use and tumor clinic pathological characteristics.Results: 1. Gastric cancer cases have more smokers and drinkers than controls and the association between them was statistically significant (P < 0.001 and P = 0.002, respectively).2. No evidence of an association between any of the four polymorphisms and gastric cancer was observed (P > 0.05) . Further analysis revealed that, when compared with the control populations, the hMSH2-118 combined variant genotypes (TC+CC) were increased the risk of gastric cancer accompanied with younger subjects (age≤63 years; adjusted odds ratios [OR] = 1.51, 95% confidence intervals [CI] = 1.05-2.16) and associated with diffuse-type tumors (adjusted OR =1.41, 95% CI = 1.01-1.96).Conclusion:1. Gastric cancer is a complex and multifactorial process. There are many known factors involved in the occurrence of gastric cancer, such as smoking and alcohol use.2. The hMLH1-93G>A, I219V and hMSH2 IVS12-6T>C polymorphisms may not contribute to risk of gastric cancer.3. The hMSH2-118T>C polymorphism may confer not only an increased risk of younger subjects (age≤63 years) of gastric cancer but also with diffuse-type tumors.