title: ERCC1 and ERCC2 variants predict survival in gastric cancer patients.
abstract: OBJECTIVE
  ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients.
  
  
  METHODS
  We genotyped by the TaqMan assay three common, potentially functional ERCC1 (rs3212986) and ERCC2 SNPs (rs13181 and rs1799793) in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes.
  
  
  RESULTS
  We found that, compared with ERCC2 rs1799793 GG+AG genotypes, the homozygous variant AA genotype was associated with significantly poorer overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56; P=0.004). In combined analyses, patients with any one of the three unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA) had statistically significant hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025), compared with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986) had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011), compared with the common haplotype G-T-G.
  
  
  CONCLUSIONS
  ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective studies are essential to confirm our findings.
authors.affiliation: Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yangkai
authors.initials: Y
authors.lastname: Li
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein
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