Association Of Polymorphisms In ERCC And XPF Genes With The Susceptibility To Gastric Cancer

Objectives The capacity of DNA repair is closely related to the susceptibility to severalof cancers. In human, there are four main pathways to repair damaged DNA. Thenucleotide excision repair (NER) is the most important DNA repair system, whichremoves a wide range of DNA lesions. The excision repair cross-complementation group1(ERCC1) and Xeroderma pigmentosum group F (XPF) has been recognized as the keyenzymes in the process of NER. By interacting with ERCC1, XPF forms a denseheterodimer and contributes to the incision of damage DNA at the5’ end during NER.This case-control study aims to investigate the association of ERCC1and XPF geneticvariations with the susceptibility to gastric cancer.Methods This study involved230gastric cancer cases from Tangshan Gongrenhospital and460cancer-free healthy controls. ERCC1-433T>C was genotyped byTaqman real-time polymerase chain reaction. The genotypes of ERCC1262G>T, XPF-673C>T, XPF11985A>G were determined by polymerase chain reaction-basedrestriction fragment length polymorphism (PCR-RFLP). Chi-square test was used tocompare the distribution of the genotypes between gastric cancer patients and healthycontrols. Odds ratios (ORs) and95%confidence intervals (CIs) were calculated bylogistic regression in order to evaluate the association of genetic variants in ERCC1andXPF genes with the risk of gastric cancer.Results Logistic regression analysis showed that ERCC1262G>T variant wasassociated with the risk of developing gastric cancer. Compared with the carrier with262GG genotype, those with262TT genotype had a decreased the risk of gastric cancerwith OR (95%CI) of0.62(0.40-0.97; P=0.037). When stratified by smoking status, the262T containing genotype was related to the risk of gastric cancer with OR (95%CI) of0.60(0.38-0.93; P=0.021) among non-smokers, but not among smokers. We didn’t findthe association of-433CT and CC genotype with the risk of gastric cancer with the OR(95%CI) of0.92(0.58-1.47) and0.68(0.18-2.63) compared with-433TT genotype. As toXPF-673C>T genetic variant, our data didn’t show any significant correlation betweenthese two polymorphisms and the susceptibility to gastric cancer. For XPF11985A>Gpolymorphism, there also had no significant difference of the genotype distribution between gastric cancer cases and controls. The OR (95%CI) for11985AG and GG are1.09(0.77-1.54) and0.66(0.30-1.45), respectively.Conclusions ERCC1262G>T polymorphism was associated with a decreased risk ofdeveloping gastric cancer in Chinese population, and the protective effect was moresignificant in non-smokers. There had no significant differences of the genotypedistribution between gastric cancer cases and controls for ERCC1-433T>C, XPF-673C>T,11985A>G polymorphism.