Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-14
pubmed:abstractText
Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1,000 biopsy specimens from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ER?) and secreted frizzled related protein-1 (SFRP1), using bisulfite pyrosequencing. We used generalized estimating equations regression analysis to examine the association between methylation and selected variables. For both ER? and SFRP1, percentage methylation was significantly higher in the rectum than in the right colon (P = 0.001). For each 10 years of age, we observed a 1.7% increase in methylation level for ER? and a 2.9% increase for SFRP1 (P < 0.0001). African Americans had a significantly lower level of ER? and SFRP1 methylation than Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ER? (P = 0.03) and SFRP1 methylation (P = 0.01). Our results suggest that CGI methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults, given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1940-6215
pubmed:author
pubmed:copyrightInfo
©2010 AACR.
pubmed:issnType
Electronic
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1552-64
pubmed:dateRevised
2011-5-20
pubmed:meshHeading
pubmed-meshheading:21149331-Adenoma, pubmed-meshheading:21149331-Colon, pubmed-meshheading:21149331-Colonic Polyps, pubmed-meshheading:21149331-Colorectal Neoplasms, pubmed-meshheading:21149331-CpG Islands, pubmed-meshheading:21149331-DNA Methylation, pubmed-meshheading:21149331-Double-Blind Method, pubmed-meshheading:21149331-Estrogen Receptor alpha, pubmed-meshheading:21149331-Female, pubmed-meshheading:21149331-Folic Acid, pubmed-meshheading:21149331-Follow-Up Studies, pubmed-meshheading:21149331-Humans, pubmed-meshheading:21149331-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:21149331-Intestinal Mucosa, pubmed-meshheading:21149331-Male, pubmed-meshheading:21149331-Membrane Proteins, pubmed-meshheading:21149331-Middle Aged, pubmed-meshheading:21149331-Placebos, pubmed-meshheading:21149331-Prognosis, pubmed-meshheading:21149331-Rectum, pubmed-meshheading:21149331-Tumor Markers, Biological
pubmed:year
2010
pubmed:articleTitle
Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa.
pubmed:affiliation
Department of Medicine, Dartmouth Medical School, Evergreen Center, Lebanon, NH 03756, USA. john.a.baron@dartmouth.edu
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Multicenter Study, Research Support, N.I.H., Extramural