title: Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan.
abstract: The aim of this study was to investigate the influence of combining thymidylate synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate and time to progression (TTP) in metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) plus irinotecan or oxaliplatin (OXA). PCR, RFLP, allelic discrimination and direct sequencing were performed to elucidate TS, XRCC1 and UGT1A1 *28 genotypes in blood from 71 patients. Patients with a number of favourable genotypes (NFG) > or =1 had a lower progression rate and a better TTP than patients with NFG=0 (log-rank p<0.03). In the OXA + 5-FU group, patients with the TS 5' single nucleotide polymorphism and/or XRCC1 genotypes favourable to treatment had a better TTP (log-rank p=0.02). The TS 5' tandem repeat polymorphism and the NFG were independent prognostic factors in the Cox-based multivariate analysis (p<0.03). These results confirm the influence on patient out-come of these genetic polymorphisms and the possibility of studying them together to predict the outcome in first-line treated colorectal cancer patients.
authors.affiliation: Medical Oncology Service, Institut Catala Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martinez-Balibrea
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Manzano
authors.forename: Anna
authors.initials: A
authors.lastname: Martinez-Cardus
authors.forename: Teresa
authors.initials: T
authors.lastname: Moran
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cirauqui
authors.forename: Silvia
authors.initials: S
authors.lastname: Catot
authors.forename: Miguel
authors.initials: M
authors.lastname: Taron
authors.forename: Albert
authors.initials: A
authors.lastname: Abad
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011755:Pyrophosphatases / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; D000077146:Irinotecan; D013940:Thymidylate Synthase; D014453:Glucuronosyltransferase; D011755:Pyrophosphatases; C023273:uridine diphosphatase; D005472:Fluorouracil; D002166:Camptothecin