Title
Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: The Netherlands cohort study on diet and cancer
Author
van Engeland, M.
Weijenberg, M.P.
Roemen, G.M.J.M.
Brink, M.
de Bruïne, A.P.
Goldbohm, R.A.
van den Brandt, P.A.
Baylin, S.B.
de Goeij, A.F.P.M.
Herman, J.G.
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 aherrant 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, p14ARF, p16INK4A, hMLH1, O6-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 p14ARF; 31% for p16INKA4A; 29% for hMLH1; 41% for O6-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.
Subject
Health
Food and Chemical Risk Analysis
alcohol
folic acid
protein p14
protein p16
adult
aged
alcohol consumption
article
cancer risk
colon carcinogenesis
colorectal cancer
controlled study
CpG island
dietary intake
DNA methylation
female
human
major clinical study
male
Netherlands
priority journal
promoter region
Aged
Alcohol Drinking
Ascorbic Acid
Cocarcinogenesis
Cohort Studies
Colorectal Neoplasms
Diet
Dietary Fiber
DNA Methylation
DNA, Neoplasm
Dose-Response Relationship, Drug
Energy Intake
Ethanol
Female
Folic Acid
Folic Acid Deficiency
Food Habits
Gene Silencing
Humans
Iron, Dietary
Male
Middle Aged
Netherlands
Pilot Projects
Promoter Regions (Genetics)
Risk Factors
To reference this document use:
http://resolver.tudelft.nl/uuid:1545d509-f701-432f-a8d3-99bf1a54e884
TNO identifier
237146
ISSN
0008-5472
Source
Cancer Research, 63 (12), 3133-3137
Document type
article