title: Polymorphisms in the base excision repair pathway modulate prognosis of platinum-based chemotherapy in advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy.
  
  
  METHODS
  We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy.
  
  
  RESULTS
  Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11-5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02-3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12-0.92).
  
  
  CONCLUSIONS
  We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.
authors.affiliation: Department of Oncology, BenQ Medical Center, Nanjing Medical University, Suzhou 215000, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Zhao
authors.forename: Lingmin
authors.initials: L
authors.lastname: Hu
authors.forename: Jiali
authors.initials: J
authors.lastname: Xu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shao
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D017671:Platinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase