Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy.

摘要: Purpose: Fluorouracil (5-FU) is widely used in the treatment of colorectal cancer. Methylenetetrahydrofolate reductase (MTHFR) could play an important role action 5-FU, inhibitor thymidylate synthetase, by converting 5,10-methylenetetrahydrofolate, a substrate to 5-methyltetrahydrofolate. A polymorphism MTHFR (677 C→T; A222V) reduces enzyme activity and presumably increases level 5,10-methylenetetrahydrofolate. This increase would be expected correlate with improved response 5-FU. The aim present study was investigate association between 5-FU other fluoropyrimidines patients metastatic Experimental design: Forty-three adenocarcinoma were analyzed. All treated p.o. or i.v. fluoropyrimidine-based chemotherapy. comprehensive chart examination performed determine tumor rates. Genomic DNA extracted from blood, genotypes determined. Results: At least one copy mutant valine allele 26 (21 heterozygotes 5 homozygotes). remaining 17 carried only alanine allele. Exploration relationship alleles rates revealed statistically significant difference frequency among responders versus nonresponders ( P = 0.0351). observation associated odds ratio 2.86 (95% confidence interval 1.06–7.73) for individuals Conclusions: Our results show link chemotherapy suggest that genotyping may predictive benefit selecting regimens.