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Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk.
Pubmed ID
23001241 (View this publication on the PubMed website)
Digital Object Identifier
Cancer Epidemiol. Biomarkers Prev. 2012 Nov; Volume 21 (Issue 11): Pages 2014-21
Huang WY, Su LJ, Hayes RB, Moore LE, Katki HA, Berndt SI, Weissfeld JL, Yegnasubramanian S, Purdue MP
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8110, MSC 7240, Bethesda, MD 20892, USA.

BACKGROUND: Systematic genome-wide reductions of methylated cytosine (5-mC) levels have been observed in colorectal cancer tissue and are suspected to play a role in carcinogenesis, possibly as a consequence of inadequate folate intake. Reduced 5-mC levels in peripheral blood leukocytes have been associated with increased risk of colorectal cancer and adenoma in cross-sectional studies.

METHODS: To minimize disease- and/or treatment-related effects, we studied leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and 493 controls who were cancer-free at blood collection from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was determined by a high-pressure liquid chromatography (HPLC)/tandem mass spectrometry method and expressed as the relative amount of methyl to total cytosine residues, or %5-mC. We estimated the association between colorectal cancer risk and %5-mC categories by computing ORs and 95% confidence intervals (CI) through logistic regression modeling.

RESULTS: We observed no dose-dependent association between colorectal cancer and%5-mC categories (lowest vs. highest tertile: OR, 1.14; 95% CI, 0.80-1.63; P(trend) = 0.51). However, among subjects whose 5-mC levels were at the highest tertile, we observed an inverse association between natural folate intake and colorectal cancer (highest tertile of natural folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; P(trend) = 0.003; P(interaction) = 0.003).

CONCLUSIONS: This prospective investigation show no clear association between leukocyte 5-mC level and subsequent colorectal cancer risk but a suggestive risk modification between 5-mC level and natural folate intake.

IMPACT: Adequate folate status may protect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome.

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