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Is there a link between genome-wide hypomethylation in blood and cancer risk?

Abstract
Cancer cells display widespread genetic and epigenetic abnormalities, but the contribution to disease risk, particularly in normal tissue before disease, is not yet established. Genome-wide hypomethylation occurs frequently in tumors and may facilitate chromosome instability, aberrant transcription and transposable elements reactivation. Several epidemiologic case-control studies have reported genomic hypomethylation in peripheral blood of cancer patients, suggesting a systemic effect of hypomethylation on disease predisposition, which may be exploited for biomarker development. However, more recent studies have failed to reproduce this. Here, we report a meta-analysis, indicating a consistent inverse association between genomic 5-methylcytosine levels and cancer risk [95% confidence interval (CI), 1.2-6.1], but no overall risk association for studies using surrogates for genomic methylation, including methylation at the LINE-1 repetitive element (95% CI, 0.8-1.7). However, studies have been highly heterogeneous in terms of experimental design, assay type, and analytical methods. We discuss the limitations of the current approaches, including the low interindividual variability of surrogate assays such as LINE1 and the importance of using prospective studies to investigate DNA methylation in disease risk. Insights into genomic location of hypomethylation, from recent whole genome, high-resolution methylome maps, will help address this interesting and clinically important question.
AuthorsKevin Brennan, James M Flanagan
JournalCancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 5 Issue 12 Pg. 1345-57 (Dec 2012) ISSN: 1940-6215 [Electronic] United States
PMID23135621 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review)
Copyright©2012 AACR
Chemical References
  • Biomarkers, Tumor
  • DNA Transposable Elements
Topics
  • Biomarkers, Tumor
  • Chromosomal Instability
  • DNA Methylation
  • DNA Transposable Elements
  • Epigenesis, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome, Human
  • Genomics
  • Humans
  • Long Interspersed Nucleotide Elements (genetics)
  • Male
  • Microsatellite Repeats
  • Models, Genetic
  • Neoplasms (blood, diagnosis, genetics)
  • Odds Ratio
  • Risk

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