In our study, we investigate the possible association of
thymidylate synthase polymorphism, 28 bp tandem repeat in 5'-UTR (transcription enhancer element) with susceptibility of colorectal and
gastric cancer in Tunisian population. Because
thymidylate synthase provides an effective prediction of
chemotherapy treatment based on
5-fluorouracil, our interest in this study was focused on finding an eventual interaction between
thymidylate synthase polymorphism and treatment of sporadic colorectal and
gastric cancer. Whole blood was collected into
EDTA tube, after centrifugation for 15 min, the buffy coat was isolated, and genotyping of TS 5'-UTR polymorphism was carried by polymerase chain reaction method using appropriate primers. Determination of the different genotypes was done directly on the stained
agarose gel. Our finding showed that the 5'tandem repeat polymorphism of the
thymidylate synthase gene is associated with risk of
colorectal cancer; thus, LL (3R/3R) genotype is significantly high in patients with
colorectal cancer compared to controls (P = 0.002; OR 2.7; 95 % CI 1.4-5.2). In addition, we found a positive association between SL (2R/3R) genotype in the
thymidylate synthase 5'-UTR and
gastric cancer risk (P = 0.015; OR 4.46; 95 % CI 1.08-19.64). Furthermore, we found a correlation of
thymidylate synthase polymorphism with the
fluorouracil-based
therapy regimes and also with preoperatory radiation in patients with
colorectal cancer.
Thymidylate synthase is associated with risk of
colorectal cancer but not with
gastric cancer; however, heterozygous SL (2R/3R) polymorphism is associated with risk of
gastric cancer; moreover, the 5' tandem repeat polymorphism of
thymidylate synthase gene was an independent predictor of the clinical treatment.