Premium
Prognostic significance of thymidylate synthase polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy
Author(s) -
Arrazubi V.,
Suárez J.,
Guerrero D.,
Gómez M.,
Viúdez A.,
Arias F.,
Balén E.,
Vera R.
Publication year - 2013
Publication title -
colorectal disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.029
H-Index - 89
eISSN - 1463-1318
pISSN - 1462-8910
DOI - 10.1111/codi.12009
Subject(s) - thymidylate synthase , medicine , colorectal cancer , chemoradiotherapy , genotype , oncology , single nucleotide polymorphism , gastroenterology , chemotherapy , allele , cancer , fluorouracil , biology , genetics , gene
Aim There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5‐fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation. Method Ninety‐nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine‐based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5′‐terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3′‐untranslated region. DNA was extracted from paraffin‐embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism. Results The 6 bp polymorphism was significantly associated with disease‐free survival (+ 6 bp/+ 6 bp vs −6 bp/−6 bp, P = 0.032 logistic regression). No differences were found in disease‐free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression. Conclusion The study suggests that the TS 6 bp polymorphism may be a predictor of disease‐free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation.