Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

Siddhartha P. Kar, Jonathan Beesley, Ali Amin Al Olama, Kyriaki Michailidou, Jonathon Tyrer, Jenny Donovan

Research output: Contribution to journalArticle (Academic Journal)peer-review

75 Citations (Scopus)
290 Downloads (Pure)

Abstract

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10-8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10-5 in the three-cancer meta-analysis.
Original languageEnglish
Pages (from-to)1052-1067
Number of pages16
JournalCancer Discovery
Volume6
Issue number9
Early online date17 Jul 2016
DOIs
Publication statusPublished - Sep 2016

Structured keywords

  • Centre for Surgical Research

Keywords

  • breast cancer
  • ovarian cancer
  • prostate cancer
  • genome-wide association studies
  • pleiotropy

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