Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk

• DOI: 10.1016/j.celrep.2014.03.016
• Publication Date: 2014-04-03T13:30:19Z
• Authors: Holger Heyn; Sergi Sayols; Catia Moutinho; Enrique Vidal; Jose V. Sanchez-Mut; Olafur A. Stefansson; Ernest Nadal; Sebastian Moran; Jorunn E. Eyfjord; Eva Gonzalez-Suarez; Miguel Angel Pujana; Manel Esteller
• Keywords: 0301 basic medicine; Polymorphism, Genetic; QH301-705.5; ADN; Quantitative Trait Loci; DNA; DNA Methylation; Methylation; 3. Good health; Epigènesi; 03 medical and health sciences; Neoplasms; Marcadors genètics; Genetic markers; Humans; Genetic Predisposition to Disease; Biology (General); Metilació; Càncer; Alleles; Cancer; Epigenesis; Genome-Wide Association Study

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.