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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics and Dietary and Genetic Factors

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 and Jean-Pierre J. Issa
Jane C. Figueiredo
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Maria V. Grau
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Kristin Wallace
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A. Joan Levine
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Lanlan Shen
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Randala Hamdan
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Xinli Chen
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Robert S. Bresalier
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Gail McKeown-Eyssen
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Robert W. Haile
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John A. Baron
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Jean-Pierre J. Issa
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DOI: 10.1158/1055-9965.EPI-08-0926 Published April 2009
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Abstract

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 ∼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 B6 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. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1041–9)

  • Global LINE-1 methylation
  • Folate
  • Folic Acid
  • Clinical Trial
  • Colon
  • Lifestyle
  • Dietary
  • Polymorphisms
  • Adenomas

Footnotes

  • ↵6 http://www.nutritionquest.com/research/validation_study_ref.htm

  • Grant support: National Cancer Institute, NIH grants R01-CA-105346, R01-CA-059005, and U54-CA-100971.

    • Accepted January 29, 2009.
    • Received October 1, 2008.
    • Revision received December 22, 2008.
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Cancer Epidemiology Biomarkers & Prevention: 18 (4)
April 2009
Volume 18, Issue 4
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Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics and Dietary and Genetic Factors
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 and Jean-Pierre J. Issa
Cancer Epidemiol Biomarkers Prev April 1 2009 (18) (4) 1041-1049; DOI: 10.1158/1055-9965.EPI-08-0926

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Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics and Dietary and Genetic Factors
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 and Jean-Pierre J. Issa
Cancer Epidemiol Biomarkers Prev April 1 2009 (18) (4) 1041-1049; DOI: 10.1158/1055-9965.EPI-08-0926
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