Methylenetetrahydrofolate Reductase Polymorphism (677 C > T) Predicts Long Time to Progression in Metastatic Colon Cancer Treated with 5-Fluorouracil and Folinic Acid

Background and Aims. Fluoropyrimidine-based chemotherapy is the most common treatment for unresectable metastatic colorectal cancer (m-CRC). Therapy with 5-FU/folinic acid (FA) continues to be a standard treatment in developing countries. Pharmacogenomics allows the tailoring of cancer therapy to the patient. The polymorphism 677C > T of the methylenetetrahydrofolate reductase (MTHFR) gene seems to influence the effectiveness of treatment with 5-FU. We undertook this study to evaluate the frequency of MTHFR 677C > T polymorphism and its relationship to the time to progression (TTP) and overall survival (OS) in m-CRC treated with 5-FU/FA. Methods. The MTHFR 677C > T polymorphism was determined using PCR and allele-specific digestion. The clinical variables, TTP and OS, were analyzed in each case and compared between wild-type and variant polymorphic groups. Results. Among 34 patients (12 males and 22 females), we detected eight wild-type homozygous patients (CC; 24%), nine variant homozygous (TT; 26%), and 17 heterozygous (CT; 50%) individuals. The median TIP in patients with the MTHFR 677 CC, CT, and TT genotypes was 3.43, 4.77, and 4.80 months, respectively (p = 0.047, log rank). A longer TTP was observed in patients with polymorphic variant (CT and TT) compared with the wild-type homozygous patients (4.80 vs. 3.43 months; p = 0.031, log rank). Conclusions. In this study, the frequency of the MTHFR 677C > T polymorphism is 50% among m-CRC Mexican patients. The results of this study appear to show that the presence of the MTHFR 677C> T polymorphism is associated with longer TTP and OS in m-CRC treated with 5-FU/FA. (C) 2010 IMSS. Published by Elsevier Inc.