title: Tumor site- and stage-specific associations between allelic variants of glutathione S-transferase and DNA-repair genes and overall survival in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy.
abstract: BACKGROUND
  Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.
  
  
  METHODS
  We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.
  
  
  RESULTS
  The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR  =1.38, 95% CI  =1.02-1.87), and rectal cancer patients had the poorest survival among them (HR  =1.87, 95% CI  =1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR  =1.69, 95% CI  =1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR  =2.60, 95% CI  =1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR  =2.77, 95% CI  =1.25-6.17).
  
  
  CONCLUSIONS
  The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.
authors.affiliation: Department of Public Health, College of Public Health, China Medical University, Taichung City, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lai
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.forename: Fung-Chang
authors.initials: FC
authors.lastname: Sung
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.forename: Chyi-Huey
authors.initials: CH
authors.lastname: Bai
authors.forename: Fang-Yang
authors.initials: FY
authors.lastname: Wu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D012189:Retrospective Studies
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005982:Glutathione Transferase; D005472:Fluorouracil
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