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Cancer Therapy: Clinical |
Authors' Affiliations: 1 Centre National de la Recherche Scientifique UPR 2169; 2 Département de Médecine; 3 Département de Pathologie; and 4 Département de Chirurgie, Institut Gustave Roussy, Villejuif, France; and 5 Institut National de la Santé et de la Recherche Médicale, Centre d'Investigation Clinique 202, Tours, France
Requests for reprints: Françoise Praz, Centre National de la Recherche Scientifique UPR 2169, "Genetic Instability and Cancer," Institut Gustave Roussy, 39 rue Camille Desmoulins, 94 800 Villejuif, France. Phone: 33-1-4211-4958; Fax: 33-1-4211-5008; E-mail: praz{at}igr.fr.
Purpose: The aim of our study was to assess whether the polymorphism of the nucleotide excision repair enzyme, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), had an effect on the tumor response in patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. We have studied the synonymous polymorphism that causes a single nucleotide change C to T at codon 118 converting a codon of common usage (AAC) to a less used codon (AAT), both coding asparagine. This change results in a decreased ERCC1 gene expression, which impairs repair activity.
Experimental Design: Ninety-one patients with a median age of 55.1 years treated for a metastatic colorectal cancer were included in our retrospective study. The ERCC1 polymorphism was analyzed in the normal tissue of all patients.
Results: Twenty (22%) were homozygous for AAC codon (C/C genotype), 30 were (33%) homozygous for AAT codon (T/T genotype), and 41 (45%) were heterozygous (C/T genotype). The objective response rate to oxaliplatin in combination with 5-fluorouracil (5-FU) was significantly higher in the T/T genotype group compared with the C/T and the C/C genotype groups (61.9%, 42.3%, and 21.4%, respectively; P = 0.018). By contrast, no significant difference was observed when patients were treated with either 5-FU alone (45%, 29.2%, and 33.3%, respectively; P = 0.407) or in combination with irinotecan (46.1%, 25.0%, and 27.3%, respectively; P = 0.305).
Conclusions: Our observations allowed us to define the first useful predictive criterion for oxaliplatin/5-FU response in patients with metastatic colorectal cancer.
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