title: ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test.
  
  
  RESULTS
  Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031-3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010-4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073-24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056-6.248; P = 0.038).
  
  
  CONCLUSIONS
  The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hekun
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Jumei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Xuping
authors.initials: X
authors.lastname: Xi
authors.affiliation: Department of Radiation Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Bingqiang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Key Laboratory of Particle and Radiation Imaging, Ministry of Education, Institute of Medical Physics and Engineering, Department of Engineering Physics, Tsinghua University, Beijing, China.
authors.forename: Jingtian
authors.initials: J
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D002277:Carcinoma; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000532:radiotherapy; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C071447:ERCC1 protein, human; D004720:Endonucleases