The role of B-vitamins-gene interactions in colorectal carcinogenesis- A molecular epidemiological approach

摘要: Folate deficiency can affect DNA methylation and synthesis. Both factors may be operative in colorectal carcinogenesis. Many enzymes, like methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine (MTR), serine hydroxymethyltransferase (SHMT), are needed for conversions folate metabolism. Flavin adenine dinucleotide, a metabolite of vitamin B2, is cofactor MTHFR; B6 SHMT; B12 MTR. Polymorphisms exist most the genes encoding enzymes that play role Therefore, genetic variation might influence synthesis processes thus This thesis describes studies have been conducted to clarify folate, related B-vitamins, In meta-analysis human observational on association between intake risk adenomas, including data from 4 cohort 10 case-control studies, pooled relative risks (95% confidence interval (CI)) highest vs. lowest exposure category 0.85 (0.71;1.01) dietary 0.75 (0.61;0.93) total were found. Dutch study, adenoma cases (n=768) endoscopy controls with no history polyps (n=709), slightly positive (odds ratio (OR) tertile 1.32, 95% CI 1.01;1.73), an inverse B2 (OR 0.51, 0.36;0.73) was found, especially among those MTHFR 677 TT genotype. A null found B12. Furthermore, combined B-vitamins important: adenomas seemed more pronounced low intakes. The polymorphisms metabolism studied ( , TS SHMT1 ) did not seem when taken into account. relatively high (>212 μ g/day) mildly inversely associated promoter six selected tumor suppressor repair tissue as compared g/day), statistically non-significant ORs ranging 0.54 0.86. effect mainly restricted carrying randomized, controlled intervention study 86 subjects dosage synthetic folic acid (5 mg/day) (1.25 months increase uracil incorporation Δ - placebo 0.45, -0.19;1.09) upmethylation 1.67, 0.95;2.95), both biomarkers measured rectal mucosa biopsies. Again, results these small suggest potential adverse should considered, administered after neoplastic lesions established. However, need confirmed by larger other populations similar intakes which C677T genotype or