title: Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment.
abstract: 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.
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, The Faculty of Sciences, Tunis El MANAR University, El MANAR Campus, 2092, Tunis, Tunisia, olfa.baroudi@yahoo.fr.
authors.forename: Olfa
authors.initials: O
authors.lastname: Baroudi
authors.forename: Thouraya
authors.initials: T
authors.lastname: Baroudi
authors.forename: Ines
authors.initials: I
authors.lastname: Omrane
authors.forename: Amel
authors.initials: A
authors.lastname: Moussa
authors.forename: Amel
authors.initials: A
authors.lastname: Mezlini
authors.forename: Hajer
authors.initials: H
authors.lastname: Ayari
authors.forename: Sami
authors.initials: S
authors.lastname: Guermazi
authors.forename: Abdesslem
authors.initials: A
authors.lastname: Bahloul
authors.forename: Hassen
authors.initials: H
authors.lastname: Bouzaienne
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.forename: Yves Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Amel Benammar
authors.initials: AB
authors.lastname: El-Gaaied
authors.forename: Karim
authors.initials: K
authors.lastname: Bougatef
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D020080:Tandem Repeat Sequences / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology
chemical_list: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil