Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients

International Journal of Cancer. Journal International Du Cancer
Eugenio MarcuelloMontserrat Baiget

Abstract

Thymidylate synthase (TS) is the primary target of 5-fluorouracil (5-FU). A VNTR polymorphism in the TS promoter region is associated with the efficacy of 5-FU-based chemotherapy in colorectal cancer. A common G>C SNP at the 12th nucleotide of the second repeat in the TS*3 alleles has been recently described. The combination of SNP and VNTR allows the definition of 3 TS alleles: *2, *3G and *3C. The aim of our study was to evaluate the predictive value of clinical response and survival of these new defined TS alleles. TS genotypes of 89 patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-based chemotherapy were carried out. The clinical outcome was evaluated according to the genotype (high expression genotype: *2R/*3G; *3C/*3G; *3G/*3G; and low expression genotype: *2R/*2R; *2R/*3C; *3C/*3C. A higher overall response was observed in the group of patients with a low expression genotype (p = 0.035). The probability of achieving a clinical response of patients with a low expression-related genotype was 2.9 higher than that of the other group (95% CI = 1.03-5.6, p = 0.04). The median time to progression was 12 months and 9 months in the low and high expression groups, respectively (p = 0.07, log rank test). Ove...Continue Reading

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