|Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.|
|PMID: 19336559 Owner: NLM Status: MEDLINE|
|BACKGROUND: Global loss of methylated cytosines in DNA, thought to predispose to chromosomal instability and aneuploidy, has been associated with an increased risk of colorectal neoplasia. Little is known about the relationships between global hypomethylation and lifestyle, demographics, dietary measures, and genetic factors.
METHODS: Our data were collected as part of a randomized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas. At a surveillance colonoscopy approximately 3 years after the qualifying exam, we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon. Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 (long interspersed nucleotide elements) repeats.
RESULTS: The analysis included data from 388 subjects. There was relatively little variability in LINE methylation overall. Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side (P < 0.0001). No significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes. Race, dietary folic acid, and plasma B(6) showed associations with global methylation that differed between the right and the left bowel. The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation, and we found no association between LINE-1 methylation and risk of adenomas.
CONCLUSIONS: LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite.
|Jane C Figueiredo; Maria V Grau; Kristin Wallace; A Joan Levine; Lanlan Shen; Randala Hamdan; Xinli Chen; Robert S Bresalier; Gail McKeown-Eyssen; Robert W Haile; John A Baron; Jean-Pierre J Issa|
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|Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural Date: 2009-03-31|
|Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 18 ISSN: 1055-9965 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2009 Apr|
|Created Date: 2009-04-09 Completed Date: 2009-06-16 Revised Date: 2013-06-05|
Medline Journal Info:
|Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States|
|Languages: eng Pagination: 1041-9 Citation Subset: IM|
|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
prevention & control
Aspirin / administration & dosage
Colon / pathology*
Colonic Polyps / pathology
Colorectal Neoplasms / epidemiology, genetics*, prevention & control
Folic Acid / administration & dosage
Long Interspersed Nucleotide Elements / genetics*
Vitamin B 6 / administration & dosage
|R01 CA059005/CA/NCI NIH HHS; R01 CA059005-10/CA/NCI NIH HHS; R01 CA059005-10S1/CA/NCI NIH HHS; R01 CA059005-16/CA/NCI NIH HHS; R01 CA105346-04/CA/NCI NIH HHS; R01-CA-059005/CA/NCI NIH HHS; R01-CA-105346/CA/NCI NIH HHS; U54 CA100971/CA/NCI NIH HHS; U54 CA100971-05/CA/NCI NIH HHS; U54-CA-100971/CA/NCI NIH HHS|
|50-78-2/Aspirin; 59-30-3/Folic Acid; 8059-24-3/Vitamin B 6|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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