Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin 5-fluorouracil as first-line chemotherapy

• Published in: British journal of cancer Vol. 99; no. 7; pp. 1050 - 1055
• Main Authors: Paré, L, Marcuello, E, Altés, A, Río, E del, Sedano, L, Salazar, J, Cortés, A, Barnadas, A, Baiget, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.10.2008; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical outcomes; Clinical Study; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease-Free Survival; DNA-Binding Proteins - genetics; Drug Resistance; Endonucleases - genetics; Epidemiology; Female; Fluorouracil - administration & dosage; Gastroenterology. Liver. Pancreas. Abdomen; Glutathione Transferase - genetics; Humans; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Male; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Organoplatinum Compounds - administration & dosage; Pharmacogenetics; Polymerase Chain Reaction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors; X-ray Repair Cross Complementing Protein 1; colorectal cancer; polymorphisms; oxaliplatin-based chemotherapy; DNA-repair genes; pharmacogenetics; Antineoplastic agent; Rectal disease; Prognosis; Genetic variability; Colorectal cancer; DNA repair; Repair gene; Cancerology; Oxaliplatin; Genetics; Intestinal disease; Advanced stage; Platinum II Complexes; Fluorouracil; Human; Pharmacogenetics; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Genotype; Malignant tumor; Thymidylate synthase; First line treatment; Colonic disease; Alkylating agent; Chemotherapy; Treatment; Antimetabolic; Methyltransferases; DNA; Pyrimidine derivatives; Digestive diseases; Predictive factor; Cancer; Polymorphism
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604671

To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 ( ERCC1 ), xeroderma pigmentosum group D ( XPD ), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1 -118 and XPD 751 polymorphisms were significant ( P =0.02 and P =0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1 -118 retained significance ( P =0.008). In the univariate analysis for PFS, ERCC1 -118 and XPD 751 were significant ( P =0.003 and P =0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS ( P =0.02). Finally, ERCC1 -118 and XPD 751 polymorphisms were significant in the univariate analysis for OS ( P =0.006 and P =0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis ( P =0.022 and P =0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments.