rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-12-14
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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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Placebos,
http://linkedlifedata.com/resource/pubmed/chemical/SFRP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/estrogen receptor alpha, human
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1940-6215
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pubmed:author |
pubmed-author:AhnenDennisD,
pubmed-author:BaronJohn AJA,
pubmed-author:BarryElizabeth LEL,
pubmed-author:ChenXinliX,
pubmed-author:GrauMaria VMV,
pubmed-author:GuiJiangJ,
pubmed-author:HaileRobert WRW,
pubmed-author:HamdanRandalaR,
pubmed-author:IssaJean Pierre JJP,
pubmed-author:LevineA JoanAJ,
pubmed-author:McKeown-EyssenGailG,
pubmed-author:ShenLanlanL,
pubmed-author:WallaceKristinK
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pubmed:copyrightInfo |
©2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1552-64
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pubmed:dateRevised |
2011-5-20
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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
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pubmed:year |
2010
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pubmed:articleTitle |
Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa.
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pubmed:affiliation |
Department of Medicine, Dartmouth Medical School, Evergreen Center, Lebanon, NH 03756, USA. john.a.baron@dartmouth.edu
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pubmed:publicationType |
Journal Article,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't,
Multicenter Study,
Research Support, N.I.H., Extramural
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