Study On Relationship Between DNA Repair Genes Polymorphism Of HOGG1, XPC, XPA And Esophageal Squamous Cell Carcinoma Susceptibility

Objective: Polymorphisms in DNA repair genes may contribute to variations in DNA repair capacity, thereby influence the individual's susceptibility to carcinogenesis. Base excision repair (BER) and nucleotide excision repair (NER) are the main DNA repair pathways. In order to examine the genetic polymorphisms in DNA repair genes involved in NER and BER pathways in the tumorigensis of esophageal squamous cell carcinoma(ESCC) , we investigated polymorphisms of three repair genes (hOGG1, XPC, XPA),and their association with ESCC risk, metastasis of esophageal cancer and histological differentiation.Method: A hospital-based case-control study was designed with 188 ESCC patients and 203 control subjects, matched on age and gender. All study subjects came from Xinxiang Henan province. Ser326Cys polymorphism in hOGG1 gene was determined by PCR-SSCP approach, while genotypes of XPC Ala499Val and XPA A23G were determined by PCR–RFLP. The results were analyzed using unconditional logistic regression for relevant covariates, adjusting for age and gender.Results: A significant association between the XPC Ala499Val polymorphism and ESCC risk was found, with adjusted odds ratios (OR) of 2.248 (P = 0.014) for the C/C genotype. The distribution of hOGG1 Ser326Cys and XPA A23G genotypes among controls were not different from that among cases. hOGG1 Ser326Cys polymorphism was associated with the third differentitation, while no association was found between the XPC Ala499Val, and XPA A23G polymorphisms and clinical characteristics of ESCC. Gene- gene interaction of hOGG1 and XPC polymorphisms increased the risk of ESCC in a super-multiplicative manner, with an OR of 4.207 (95% CI=1.159~15.267) for the presence of both hOGG1 C/C and XPC T/T genotypes, although the hOGG1 polymorphism itself was not associated with the risk of ESCC. No other interactions of gene-gene polymorphism were found.Conclusions: Cys/Cys genotype in hOGG1 gene plays an important role in the differentiation of ESCC. The XPC 499Ala→Val polymorphism plays an important role in the development of ESCC, and the hOGG1 326Ser→Cys polymorphism may serve as a risk modifier. The association between BER-NER interactions and the risk of ESCC was not identified in this study. Thereby a larger sample with thousands of subjects and muti-gene polymorphisms are required.