title: Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy.
abstract: BACKGROUND
  Single nucleotide polymorphism (SNP) in DNA repair genes can be used to explain the differences in survival of platinum-treated non-small cell lung cancer (NSCLC) patients regardless of their performance status. To define the role of DNA repair gene SNPs in NSCLC patients, we investigated the association between survival and 12 different SNPs of 9 DNA repair genes.
  
  
  METHODS
  340 patients were treated with platinum-based chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probe, using genomic DNA extracted from peripheral blood samples. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables.
  
  
  RESULTS
  The median overall survival time was 15 months and it was significantly longer in patients harboring ERCC1 118 C/T or T/T allele: 18 months as compared to 13.8 months for the C/C allele (P=0.014). Subgroup analysis revealed that ERCC1 118 C/T or T/T was associated with increased survival in elderly patients (P=0.018), male (P=0.022), squamous carcinoma (P=0.003), smoker (P=0.076) and those treated with non-gemcitabine/cisplatin or carboplatin (non-GP/GC) regimen (P=0.023). XRCC3C/C was associated with better survival in non-gemcitabine/cisplatin treated patients (P=0.014). Both of CCNH-V270A C/C or C/T and XPD 751 A/A showed a significant longer survival in the squamous cell carcinoma subgroup (P=0.047 and P=0.034 respectively).
  
  
  CONCLUSIONS
  Present data indicates that ERCC1 118 C/T or T/T might provide a better prognostic predictive marker of NSCLC patients treated with platinum-based chemotherapy, mainly in elderly subgroup, male, squamous carcinoma, smoker and those treated with non-GP/GC regimen.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University, No 507 Zhengmin Road, Shanghai 200433, People's Republic of China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.forename: Songwen
authors.initials: S
authors.lastname: Zhou
authors.forename: Fengyin
authors.initials: F
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianfang
authors.initials: J
authors.lastname: Xu
authors.forename: Meijun
authors.initials: M
authors.lastname: Lv
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012044:Regression Analysis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine