title: Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in non-small-cell lung cancer patients treated with gemcitabine/platinum.
abstract: BACKGROUND
  Elevated DNA-repair capacity has been related to chemoresistance of platinum doublet chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated whether single nucleotide polymorphisms of DN- repair genes excision repair cross-complementing group 1 (ERCC1), ERCC2, x-ray repair cross-complementing group 1 (XRCC1), XRCC3, and RRM1 associate with treatment outcome in NSCLC patients receiving gemcitabine plus platinum as their first-line chemotherapy.
  
  
  METHODS
  Genotyping for eight polymorphisms in five DNA-repair genes was performed with the GenomeLab nucleotide polymorphismstream Genotyping System in 62 advanced NSCLC patients in a training set and 45 patients in a validation set treated with gemcitabine/platinum.
  
  
  RESULTS
  In the training set, the wild-type genotype of XRCC1 Arg399Gln (G/G) was associated with decreased median overall survival (OS) (22 months, 95% confidence interval [CI], 10-34 months versus not reached, log-rank test, p = 0.005) than those carrying variant genotypes (G/A+A/A). In addition, there was a statistically significant longer median OS in patients carrying wild-type ERCC2 Asp312Asn genotype (G/G) (51 months, 95% CI, 19-82 months versus 10 months, log-rank test, p < 0.001) than those carrying heterozygous variant genotypes (G/A). In the multivariate Cox model, we found a significant effect of XRCC1 Arg399Gln (G/A+A/A versus G/G, hazard ratio [HR] 0.290; 95%CI, 0.12-0.705, p = 0.006) and ERCC2 Asp312Asn (G/A versus G/G, HR 14.04; 95% CI, 2.253-87.513, p = 0.005) polymorphisms on patients' OS. In the validation set, only XRCC1 399
  
  
  CONCLUSIONS
  Genetic polymorphism of XRCC1 Arg399Gln may be a candidate for contributing interindividual difference in the OS of gemcitabine/platinum-treated advanced NSCLC patients.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Liao
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Yu-Kai
authors.initials: YK
authors.lastname: Cheng
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D015996:Survival Rate / Q000639:trends; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D003841:Deoxycytidine; D010984:Platinum; D012264:Ribonucleotide Reductases; D000093542:Gemcitabine