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Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer.
- Source :
-
Cancer research [Cancer Res] 2003 Jun 15; Vol. 63 (12), pp. 3133-7. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Aged
Alcohol Drinking adverse effects
Alcohol Drinking epidemiology
Ascorbic Acid
Cocarcinogenesis
Cohort Studies
Colorectal Neoplasms etiology
Colorectal Neoplasms genetics
Dietary Fiber
Dose-Response Relationship, Drug
Energy Intake
Ethanol adverse effects
Feeding Behavior
Female
Folic Acid administration & dosage
Folic Acid Deficiency epidemiology
Humans
Iron, Dietary
Male
Middle Aged
Netherlands epidemiology
Pilot Projects
Risk Factors
Colorectal Neoplasms epidemiology
DNA Methylation drug effects
DNA, Neoplasm drug effects
Diet
Ethanol pharmacology
Folic Acid pharmacology
Gene Silencing drug effects
Promoter Regions, Genetic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 63
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 12810640