Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment

• Published in: Medical oncology (Northwood, London, England) London, England), 2014-02, Vol.31 (2), p.825, Article 825
• Main Authors: Baroudi, Olfa, Baroudi, Thouraya, Omrane, Ines, Moussa, Amel, Mezlini, Amel, Ayari, Hajer, Guermazi, Sami, Bahloul, Abdesslem, Bouzaienne, Hassen, Uhrhammer, Nancy, Bignon, Yves Jean, El-Gaaied, Amel Benammar, Bougatef, Karim
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Case-Control Studies; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - etiology; Colorectal Neoplasms - pathology; Female; Fluorouracil - therapeutic use; Follow-Up Studies; Genotype; Hematology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oncology; Original Paper; Pathology; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Prognosis; Promoter Regions, Genetic - genetics; Risk Factors; Stomach Neoplasms - drug therapy; Stomach Neoplasms - epidemiology; Stomach Neoplasms - etiology; Stomach Neoplasms - pathology; Tandem Repeat Sequences - genetics; Thymidylate Synthase - genetics; Tunisia - epidemiology
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-013-0825-z

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.