A polymorphism of the XRCC1 gene predicts for response to platinum based treatment in advanced colorectal cancer.
Recently, it has been demonstrated that the Arg399Gln substitution in the XRCC1 gene is associated with increased levels of markers of DNA damage. Deficiency in DNA repair pathways has been shown to confer to resistance to several drugs, including platinum compounds. Here we have studied whether this polymorphism of the XRCCI gene will predict response and survival of patients with metastatic colorectal cancer treated with oxaliplatin and 5-FU. Sixty-one patients received a combination of 130 mg/m2 oxaliplatin and continuous infusion 5-FU. The XRCC1 polymorphism was evaluated using a RFLP method. We found 73% (8/11) of responders had an Arg/Arg genotype and three were heterozygous, but 66% (33/50) of non-responders showed a Gln/Gln or Gln/Arg genotype (p=0.038). Patients carrying at least one Gln mutant allele were at a 5.2 (95%CI: 1.21,22.07) fold increased risk to fail the 5-FU/oxaliplatin chemotherapy. The data suggest that the polymorphism in exon 10 of the XRCC1 gene may be associated with resistance to oxaliplatin/5-FU chemotherapy in advanced colorectal cancer.
Stoehlmacher
J
J
University of Southern California Norris Comprehensive Cancer Center, Los Angeles 90033, USA.
Ghaderi
V
V
Iobal
S
S
Groshen
S
S
Tsao-Wei
D
D
Park
D
D
Lenz
H J
HJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016019:Survival Analysis; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D003062:Codon; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin