Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer.
Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aberrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14(ARF), p16(INK4A), hMLH1, O(6)-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14(ARF); 31% for p16(INK4A); 29% for hMLH1; 41% for O(6)-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.
van Engeland
Manon
M
The Research Institute GROW, Department of Pathology, University Maastricht, 6200 MD Maastricht, The Netherlands.
Weijenberg
Matty P
MP
Roemen
Guido M J M
GM
Brink
Mirian
M
de Bruïne
Adriaan P
AP
Goldbohm
R Alexandra
RA
van den Brandt
Piet A
PA
Baylin
Stephen B
SB
de Goeij
Anton F P M
AF
Herman
James G
JG
D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D001205:Ascorbic Acid; D003043:Cocarcinogenesis; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004032:Diet; D004043:Dietary Fiber; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005247:Feeding Behavior; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000453:epidemiology; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D019266:Iron, Dietary; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010865:Pilot Projects; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012307:Risk Factors
D004273:DNA, Neoplasm; D004043:Dietary Fiber; D019266:Iron, Dietary; D000431:Ethanol; D005492:Folic Acid; D001205:Ascorbic Acid