Linkage of DNA methylation quantitative trait loci to human cancer risk

Abstract

Epigenetic regulation and, in particular, DNA methyl- ation 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 power- ful 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 pri- mary human tumors, representing 13 solid cancer

types. We provide a comprehensive meQTL catalog

containing DNA methylation associations for 21%

of interrogated cancer risk polymorphisms. Differen- tially 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.