Epigenetic epidemiology for cancer risk: harnessing germline epigenetic variation

Methods in Molecular Biology
Kevin Brennan, James M Flanagan

Abstract

Genetic epidemiology aims to use the natural variation in the genome, namely single nucleotide polymorphisms and copy number variants to look for associations between particular genotypes and disease risk or prognosis. Recent work is now aiming to look further into the genome at the natural variation present in the epigenome, in DNA methylation as well as histone modifications, which both regulate gene expression. Epigenetic epidemiology aims to address the same questions about disease risk and prognosis using the normal epigenetic variability. Some examples of rare "epimutations" that can be detected in peripheral blood DNA have been reported in the genes MLH1, MSH2 and IGF2. Other studies have reported increased cancer risk with skewed distributions of the normal pattern in cancer cases compared to controls, showing the promise of harnessing the normal variation in the epigenome. However, some confounding factors need to be considered including the relationship between the epigenome and increasing age and tissue heterogeneity. Future studies using genome-wide approaches will likely find many more novel epigenetic biomarkers for cancer risk and prognosis.

Citations

Dec 18, 2012·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Mukesh VermaJohn P A Ioannidis
Apr 30, 2014·BMC Medical Genomics·Brooke L FridleyEllen L Goode
Apr 6, 2016·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Ann DavisPaolo Boffetta
Feb 28, 2013·Environmental and Molecular Mutagenesis·Scott M Langevin, Karl T Kelsey
Jan 18, 2014·Environmental and Molecular Mutagenesis·Liqiong GuoAndrea A Baccarelli
Nov 9, 2012·Cancer Prevention Research·Kevin Brennan, James M Flanagan
Nov 6, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·James M FlanaganMontserrat Garcia-Closas

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