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| Genetic and environmental factors | Epigenetic changes in CRC |
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| TYMS 28 bp 3R/3R genotype | Associated with CIMP−CRC |
| MTHFR 677TT + 1298 CC genotypes/adequate folate intake | Reduced MSI CRC risk |
| MTHFR AC or CC genotype, low folate and methionine, high alchol | Associated with CIMP+ CRC risk |
| TCNII 776G variant | Reduced CIMP+ CRC risk |
| MTHFR 677CT genotype | Decreased MGMT promoter hypermethylation |
| MTR A2756G | Reduced CIMP CRC risk, among men |
| MTRR A66G | Reduced MLH1 methylation |
| DNMT -149TT | Reduced risk proximal CRC (principally CIMP+ tumour) |
| High serum folate/vitB12 | Associated with P16 promoter methylation and with MLH1, MLH2 promoter methylation(trend) |
| Choline deficiency | Reduced CDKN3 promoter methylation |
| Low folate/High alcohol | Increased APC 1A, P14, MLH1, MGMT, and RASSF1A promoter methylation (trend) |
| Alchol (murine studies) | Reduced MTR levels/DNA hypomethylation |
| Tobacco | Reduced methylation levels of MGMT, RAR-b, and SST genes |
| Heavy smokers/low folate/low fiber intake/long-term alcohol consumption | Increased CIMP+ CRC risk (trend) |
| Green tea | Demethylation of MLH1, MGMT, and P16 genes |
| Energy restriction | Decreased CIMP+ CRC |
| Higher dietary fiber | Reduced risk CIMP+ CRC/restore protein acetylation (p53, Sp1, Sp3) |
| Obesity | Increased CIMP-low CRC, not CIMP high CRC |
| Physical activity/use NSAIDs | Reduced CIMP-low and CIMP-high CRC |
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