Integrative eQTL-based analyses reveal the biology of breast cancer risk loci

Cell. 2013 Jan 31;152(3):633-41. doi: 10.1016/j.cell.2012.12.034.

Abstract

Germline determinants of gene expression in tumors are infrequently studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL)-based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTLs accounted for 1.2% of the total variation of tumor gene expression, while somatic copy-number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in the discovery of three variants that are significantly associated with transcript levels (false discovery rate [FDR] < 0.1). Our trans-based analysis identified an additional three risk loci to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Quantitative Trait Loci*