Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA methyltransferase enzyme (DNA MTase) catalyzes DNA methylation at cytosines in CpG dinucleotides. 5-Methylcytosine modification of DNA is important in gene regulation, DNA replication, chromatin organization and disease. Increased levels of DNA MTase have been associated with the initiation and promotion of cancer. This study was conducted to assess whether cigarette smoking and other factors, such as age and gender, influence DNA MTase expression in nontumorous tissue. DNA MTase was significantly (p<0.05) higher in samples from cigarette smokers; the mean level of DNA MTase mRNA was almost 2-fold higher in these samples than in those from nonsmokers. Levels of DNA MTase mRNA were higher in samples from females than in those from males, but the difference was not statistically significant. Age was not associated with DNA MTase levels. Increased levels of DNA MTase in individuals who smoke may indicate a greater susceptibility to the risk of cancer since increased levels of this enzyme are found in cancer cell lines and human tumors. The results of this study suggest that further investigations of increased expression of this enzyme as a predisposing factor for cancer susceptibility are needed.
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PMID:Increased expression of hepatic DNA methyltransferase in smokers. 1081 34

Several observations suggest a role for DNA methylation in cancer pathogenesis. Although both selenium and folate deficiency have been shown to cause global DNA hypomethylation and increased cancer susceptibility, the nutrients have different effects on one-carbon metabolism. Thus, the purpose of this study was to investigate the interactive effects of dietary selenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were fed diets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mg folate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wk experiment, 19 rats/diet were injected intraperitoneally with dimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline. Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations. Folate deficiency increased (P < 0.05) the number of aberrant crypts per aberrant crypt foci, the concentration of colonic S-adenosylhomocysteine and the activity of liver cystathionine synthase. Selenium and folate interacted (P < 0.0001) to influence one-carbon metabolism and cancer susceptibility such that the number of aberrant crypts and the concentrations of plasma homocysteine and liver S-adenosylhomocysteine were the highest and the concentrations of plasma folate and liver S-adenosylmethionine and the activity of liver methionine synthase were the lowest in rats fed folate-deficient diets and supplemental selenium. These results suggest that selenium deprivation ameliorates some of the effects of folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione.
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PMID:Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. 1294 86

Numerous studies have explored the association of polymorphisms in the DNA methyltransferase 3b (DNMT3B) gene with the risk of different types of cancer, but yielded controversial results. Therefore, we performed a meta-analysis to derive a more precise estimation of the association between three widely-studied DNMT3B polymorphisms and overall cancer susceptibility. Totally, 4 studies with 1234 cases and 1337 controls were eligible for DNMT3B -283 T > C (rs6087990), 19 studies with 5332 cases and 7407 controls for DNMT3B -149 C > T (rs2424913), and 14 studies with 3933 cases and 4436 controls for DNMT3B -579 G > T (rs1569686). Overall, DNMT3B -283 T > C was associated with a significantly reduced risk of overall cancer (T vs. C: OR = 0.84, 95% CI = 0.71-0.99, P = 0.039). Likewise, the association of DNMT3B -579 G > T with a decreased overall cancer risk was also observed (heterozygous: OR = 0.77, 95% CI = 0.65-0.91, P = 0.003 and dominant: OR = 0.80, 95% CI = 0.66-0.98, P = 0.029); in the subgroup analysis, the protective association was found for lung and colorectal cancer, but not for head and neck cancer. Finally, the pooled analysis showed no significant association between DNMT3B -149 C > T and overall cancer susceptibility, but stratification analysis indicated that this polymorphism decreased the risk of developing head and neck cancer (heterozygous: OR = 0.73, 95% CI = 0.59-0.90, P = 0.003 and dominant: OR = 0.76, 95% CI = 0.61-0.93, P = 0.009). In conclusion, our results suggested that DNMT3B -283 T > C and DNMT3B -579 G > T but DNMT3B -149 C > T might confer protection against overall cancer risk. In the future, large and well-designed case-control studies are needed to validate our findings.
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PMID:Association of DNMT3B -283 T > C and -579 G > T polymorphisms with decreased cancer risk: evidence from a meta-analysis. 2655 Feb 25