The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

Abstract

Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex-and age-matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.

Polymorphisms of multiple genes involved in NER pathway predict prognosis of gastric cancer

“…The results for ERCC2 rs50871 was opposite to the previous findings in melanoma [25] or head and neck cancer [26], in which the GG genotype was related to favorable survival. ERCC6 rs1917799 was previously linked to increased risk of GC [27], but its role in GC prognosis has not been studied before. In this study, ERCC6 rs1917799 heterozygote GT was firstly found to be associated with significantly shorter OS than wild-type TT.…”

Epistatic SNP interaction of ERCC6 with ERCC8 and their joint protein expression contribute to gastric cancer/atrophic gastritis risk

“…In our previous pilot study, three potential functional SNPs, ERCC6 rs1917799, ERCC8 rs158572 and rs158916 were detected and two of them were supposed to be associated with GC risk [10, 11]. In the current study, we further analyzed the interaction effect of the SNPs, and found that ERCC6 rs1917799 and ERCC8 rs158572 polymorphisms were associated with CAG and GC.…”

“…Population-based epidemiologic studies have shown that ERCC6 and ERCC8 polymorphisms have a significant impact on the risk of some human malignancies, including gastric cancer [10, 11, 16, 28–30]. In vitro evidence indicated that ERCC6 polymorphisms may alter protein function [16, 31], and reduced ERCC6 protein levels were associated with increased cancer risk [32, 33].…”

“…In our previous study, we systematically analyzed the association of 43 SNPs of ten key NER pathway genes including ERCC6 , ERCC8 with survival of gastric cancer (GC) patients [9], and found that ERCC6 SNP could predict GC prognosis. Moreover, ERCC6 rs1917799 and ERCC8 rs158572 polymorphisms were associated with increased GC risk separately [10, 11]. However, it is unclear whether there are interactions among ERCC6 and ERCC8 SNPs, by which it may enhance the risk warning for GC or its precancerous diseases because SNP-SNP interactions could be more valuable than a single SNP in cancer prediction [12–14].…”

The 765G>C Polymorphism in the Cyclooxygenase-2 Gene and Gastric Cancer Risk: an Update by Meta-analysis

“…There is individual susceptibility to GC even with the same environmental exposure. Genetic factors, including variants in genes involved in the pathogenesis of GC :http://dx.doi.org/10.7314/APJCP.2014.15.6.2863 The 765G>C Polymorphism andGastric Cancer Risk-a Meta-analysis may contribute to these differences (Goto et al, 2005;Shibata et al, 2010;Sethi et al, 2012;Liu et al, 2013;Chen et al, 2014;Li et al, 2014). Therefore, during the past 10 years, genetic susceptibility evoked researchers' interest, and studies concerning polymorphisms of genes involved in the pathogenesis of GC are expanding each year.…”