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 |