title: Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer.
abstract: We performed a study to investigate the role of ERCC1, ERCC2, ERCC5, XPA and XPC polymorphisms from perspective of the whole NER pathway in the prognosis of gastric cancer. A total of 410 gastric cancer patients were recruited between January 2010 and December 2011. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to analyze genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and s1799793, ERCC5 rs17655, XPA rs1800975 and XPC rs2228001. Our study found that carriers of ERCC1 rs3212986 TT genotype showed significantly favorable survival than wide-type GG genotype in multivariate analysis (OR=6.38, 95% CI=2.54-19.03), and patients with variant CC genotype of ERCC2 rs13181 exhibited better response to chemotherapy than those with AA genotype (OR=2.21, 95% CI=1.17-4.25). By Cox proportional hazards model, patients with variant TT genotype of ERCC1 rs3212986 exhibited longer PFS and OS than those who had GG genotype (for PFS, HR=0.37, 95% CI=0.17-0.75; for OS, HR=0.36, 95% CI=0.13-0.87). For ERCC2 rs13181 polymorphism, carriers with CC genotype demonstrated significantly increased hazards of progression of disease and death in multivariate model (for PFS, HR=0.48, 95% CI=0.26-0.88; for OS, HR=0.44, 95% CI=0.20-0.91). In conclusion, our finding suggests that ERCC1 rs3212986 and ERCC2 rs13181 gene polymorphism could influence the response to chemotherapy and clinical outcome of gastric cancer.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Xue
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Chao-Xian
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Second Hospital, Shandong University Jinan 250033, China.
authors.forename: Kong-Xi
authors.initials: KX
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D054458:Amplified Fragment Length Polymorphism Analysis; D014408:Biomarkers, Tumor / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: DNA repair gene; clinical outcome; gastric cancer; polymorphism