title: Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.
abstract: Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).
  
  
  
  The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.
  
  
  
  We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.
  
  
  
  SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.|Department of Oncology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.|Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Mengyun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China. xiangjiaqing2015@sina.com.|Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. xiangjiaqing2015@sina.com.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China. qingyi.wei@duke.edu.|Duke Cancer Institute, Duke University Medical Center, 10 Bryn Searle Dr., Durham, NC, 27710, USA. qingyi.wei@duke.edu.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004260:DNA Repair / Q000235:genetics*; D003710:Demography; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012372:ROC Curve
chemical_list: D010984:Platinum
keywords: Biomarker; DNA repair; Esophageal squamous cell cancer; Platinum-based adjuvant chemotherapy; Polymorphism; Prognosis