Study On The Association Between The Variations Of HMYH And HOGG1Gene And Gastric Cancer And Colorectal Cancer And The Mechanism Of These Variations On The Gene Function

Part One:Effects of Base Excision Repair Gene hOGG1and hMYH genes Polymorphisms on colorectal cancer in the Chinese populationColorectal cancer is one of the most common cancers in the world and among the leading causes of death. The aim of this study is to investigate whether AluYb8insertion and p.Gln324His variations of human MutY homolog(hMYH) gene and p.Ser326Cys variation and5’UTR of the human oxoguanine glycosylase1(hOGG1) gene are related to the risk of colorectal cancer in the Chinese population.381colorectal cancer patients,554healthy controls were recruited to screen for these variations. Agarose gels assay was employed to discriminate genotypes of AluYb8hMYH polymorphism. High resolution melting curve analysis and sequencing were used to decide the genotype fo hOGGl5’UTR. Unlabeled probe high resolution melting curve was employed to screen for p.Gln324His variations of hMYH gene and p.Ser326Cys variation of hOGG1geneThe case-control study indicated that AluYb8MYH carriers were markedly associated with colorectal cancer (P=0.011). Four variants c.-53G>C, c.-45G>A, c.-23A>G and c.-18G>T, were detected in the5’-UTR of the hOGG1gene. The hOGG15’UTR variations, p.Ser326Cys and hMYH gene p.Gln324His didn’t show a correspondence with colorectal cancer. In summary the variant AluYb8hMYH is a risk factor for colorectal cancer.Part Two:Effects of hOGG1and hMYH gene polymorphisms on gastric cancer in the Chinese population.The incidence and mortality of gastric cancer is among the highest malignant tumors in China. The aim of this study is to investigate whether variations of the hOGG1gene and hMYH gene are related to the risk of gastric cancers in the Chinese population.There were622gastric cancer patients and932healthy controls recruited to screen for variations in the5’UTR and to screen for the missense mutation (p.Ser326Cys) in exon7of the hOGG1gene and p. Gln324His using high resolution melting curve analysis (HRM) and subsequent sequencing. The promoter luciferase activity assay was applied to assess the potential influence of the detected variants on gene function.The case-control study indicated that the c.-53G/C herterozygous genotype was markedly associated with gastric cancer (P=0.008, OR=2.304,95%CI,1.258-4.221). The clinicopathological association analysis showed that the variant of c.-53G>C in the hOGG1gene was prevalent in low differentiation patients (P=0.012, OR=3.174,95%CI:1.352-7.448). This variant decreased the gene promoter activity by approximately17.8%(P=0.041) and exhibited a synergistic effect with the missense mutation p.Ser326Cys of hOGG1by enhancing susceptibility to gastric cancers.The variant c.-53G>C in the5’-UTR of the hOGGl gene is a risk factor for gastric cancer and is potentially associated with low differentiation degree in the Chinese population.In summary, our work found that AluYb8hMYH insertion was related to colorectal cancer, and the work also indicated that c.-53G>C mutation was related to gastric cancer in the Chinese population. The different result showed that the mutation of hOGG1gene and hMYH gene can suggest different disease.