title: Methylenetetrahydrofolate reductase and methionine synthase polymorphisms and risk of bladder cancer in a Tunisian population.
abstract: Folate insufficiency can induce carcinogenesis by decreasing DNA methylation. It is well known that DNA hypomethylation is a common feature in a number of cancers. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are enzymes that play central roles in the folate metabolic pathway. Two common polymorphisms in the MTHFR gene (C677T and A1298C) and one in the MS gene (A2756G) are associated with decreased enzymatic activity. In this work, we have conducted a case-control study to assess the role of these three polymorphisms in bladder cancer development in North Tunisia. For MS A2756G, gene and genotypic distributions differed significantly between cases and controls. Furthermore, individuals carrying at least one copy of the variant allele presented a 2.33 times increased risk of developing bladder cancer than their control group [P = 0.001, odds ratio (OR) = 2.33; 95% confidence interval (CI) 1.34-4.06]. Statistically significant odds ratios were also found in patients heterozygous for MTHFR A1298C, who have a 1.8-fold higher risk of developing bladder cancer (P = 0.03, OR = 1.86; CI 95% 1.04-3.33). While the isolated polymorphism C677T did not appear to influence bladder cancer susceptibility, results suggest that it might act with an additive contribution determined by variation at MTHFR A1298C. Identical cumulative effect was detected for the MTHFR A1298C and MS 2756 genotypes. Patients harboring at least one mutant allele for each of the three positions analyzed showed a 4.76-fold increased risk of developing bladder cancer in comparison to their reference group (P = 0.02, OR = 4.76; CI 95% 1.26-17.98).
authors.affiliation: Laboratory of Genetic, Immunology and Human Pathology, Faculty of Sciences of Tunis, El Mannar I, 2092 Tunis, Tunisia. slah_mekni@yahoo.fr
authors.forename: Slah
authors.initials: S
authors.lastname: Ouerhani
authors.forename: Elisabete
authors.initials: E
authors.lastname: Oliveira
authors.forename: Raja
authors.initials: R
authors.lastname: Marrakchi
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Ben Slama
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sfaxi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ayed
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chebil
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Amel Benammar
authors.initials: AB
authors.lastname: El Gaaied
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Prata
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D014416:Tunisia; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase