1. ¹Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain
2. ²Department of Clinical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain
3. ³Department of Hematology, Fundació Althaia, Manresa, Spain
4. ⁴Center for Biomedical Research on Rare Diseases (CIBERER), Barcelona 08025, Spain

Correspondence: Dr M Baiget, Servei de Genètica. Hospital de la Santa Creu i San Pau, Pare Claret 167, Barcelona 08025, Spain. E-mail: mbaiget@santpau.es

Received 3 July 2008; Revised 18 August 2008; Accepted 22 August 2008; Published online 16 September 2008.

Abstract

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.