Combined effect of NAT2, MTR and MTHFR genotypes and tobacco on bladder cancer susceptibility in Tunisian population
| Autor: | Mohamed Riadh Ben Slama, Raja Marrakchi, Amel Benammar Elgaaied, Slah Ouerhani, Mohamed Sfaxi, Mohamed Chebil, Kamel Rouissi |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Tunisia Genotype Arylamine N-Acetyltransferase Biology medicine.disease_cause 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Gene Frequency Risk Factors Internal medicine medicine Humans Genetic Predisposition to Disease Methionine synthase Allele Methylenetetrahydrofolate Reductase (NADPH2) Carcinogen Aged Genetics Bladder cancer Smoking Case-control study DNA Methylation Middle Aged medicine.disease Endocrinology Urinary Bladder Neoplasms Oncology Case-Control Studies Methylenetetrahydrofolate reductase biology.protein Female Carcinogenesis |
| Zdroj: | Cancer Detection and Prevention. 32:395-402 |
| ISSN: | 0361-090X |
| Popis: | Background : Cigarette smoking is the predominant risk factor for bladder cancer. This risk may be modified by polymorphisms in carcinogens metabolism genes; including those involving the N-acetyl transferase 2 ( NAT2 ) which have been correlated with decreased enzyme activities. Moreover, folate insufficiency can induces carcinogenesis by decreasing DNA methylation. Methylenetetrahydrofolate reductase ( MTHFR ) and methionine synthase ( MTR ) are enzymes that play central roles in the folate metabolic pathway. The MTHFR 677*T and MTR 2756*G variants are associated with decreased enzyme activity. Methods : In this work, we have conducted a case-control study in order to assess the combined effect of tobacco, slow NAT2 variants, MTHFR 677*T and MTR 2756*G alleles on bladder cancer development in North Tunisia. Results : For MTR A2756G , alleles and genotypic distributions differed significantly between cases and controls ( p =0.00009, OR=3.27, CI 95% 1.76–6.12). While, in non-smokers patients the slow NAT2 did not appear to influence bladder cancer susceptibility; our results suggested that it might act with an additive contribution with tobacco as well as with that determined by MTR 2756 AG or 2756 GG genotypes ( p =0.0008). Identical cumulative effect was detected for slow NAT2 and MTHFR 677*T variant ( p =0.0003; OR=36.6; CI 95% 3.4–935.3). Conclusion : The strongest result obtained by this study was for an additive effect between smoking status, slow NAT2 variants, MTR 2756*G and MTHFR 677*T alleles, in affecting bladder cancer risk. |
| Databáze: | OpenAIRE |
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