Linkage of DNA methylation quantitative trait loci to human cancer risk.

Cell Rep 2014 Apr 3;7(2):331-338. Epub 2014 Apr 3.

Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain; Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08036 Barcelona, Catalonia, Spain; Instituci├│ Catalana de Recerca i Estudis Avan├žats (ICREA), 08010 Barcelona, Catalonia, Spain. Electronic address:

Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL) have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts. We propose that interrogating the interplay between polymorphic alleles and DNA methylation is a powerful method for improving our interpretation of risk alleles identified in genome-wide association studies that otherwise lack mechanistic explanation. We integrated patient cancer risk genotype data and genome-scale DNA methylation profiles of 3,649 primary human tumors, representing 13 solid cancer types. We provide a comprehensive meQTL catalog containing DNA methylation associations for 21% of interrogated cancer risk polymorphisms. Differentially methylated loci harbor previously reported and as-yet-unidentified cancer genes. We suggest that such regulation at the DNA level can provide a considerable amount of new information about the biology of cancer-risk alleles.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2014.03.016DOI Listing
April 2014
112 Reads

Publication Analysis

Top Keywords

dna methylation
24
cancer risk
12
quantitative trait
8
regulation dna
8
methylation quantitative
8
trait loci
8
methylation
6
dna
6
cancer
5
harbor reported
4
association studies
4
genome-wide association
4
patient cancer
4
integrated patient
4
studies lack
4
mechanistic explanation
4
loci harbor
4
methylated loci
4
lack mechanistic
4
explanation integrated
4

Similar Publications