Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 3680
© 2004 American Society of Clinical Oncology

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Abstract

Predictive value of single nucleotide polymorphisms (SNPs) in DNA repair genes in non-selected advanced colorectal cancer (CRC) patients (p) treated with oxaliplatin (OXA) plus 5-Fluorouracil (5-FU) first-line chemotherapy (CT)

Hospital Universitari Germans Trias i Pujol, Badalona, Spain

3680

Background: OXA cause DNA cross-linking and oxidative damage. SNPs in DNA repair genes are associated with inter-individual differences in DNA repair capacity and can explain the heterogeneity in OXA response. We assessed SNPs in four DNA repair genes belonging to three of the major DNA repair pathways: nucleotide excision repair (XPD Lys751Gln; ERCC1 C118T); base excision repair (XRCC1Arg399Gln) and homologous recombination repair (XRCC3Thr241Met) and correlated the results with outcome in OXA/5FU-treated advanced CRC p. Methods: 39 consecutive advanced CRC p were included. TaqMan 5' nuclease assay was used to examine SNPs from DNA isolated from peripheral blood lymphocytes. Results: p characteristics: median age: 59 years (33–72); 59% male. Overall outcome: median time to progression (TTP): 7 months (m); overall response rate (OR): 46%. Homozygosity for wild type alleles (Lys, C, Arg and Thr, respectively) was considered a favorable genotype for OXA response. OR according to genotype (favorable/unfavorable): XPD23 47.8/43.8%; ERCC1 33,3/47,2%; XRCC1 47.4/45% and XRCC3 44.4/38.1% (P=ns). No differences in TTP according to single genotype were observed. In contrast, when we analyzed the impact of allele combination, p carrying 4 or more unfavorable alleles (47% p) had a shorter TTP than those carrying less than 4 (53% p) (4.5m vs 7.5m; P=0.07). Conclusions: The impact of allele combination in DNA repair genes may be a key predictive marker of chemosensitivity. The prospective inclusion and genotyping of advanced CRC p is needed to clarify the role of these SNPs in predicting response to OXA/5FU.

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