Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Research output: Contribution to journalJournal articleResearchpeer-review

  • Siddhartha P Kar
  • Jonathan Beesley
  • Ali Amin Al Olama
  • Kyriaki Michailidou
  • Jonathan Tyrer
  • ZSofia Kote-Jarai
  • Kate Lawrenson
  • Sara Lindstrom
  • Susan J Ramus
  • Deborah J Thompson
  • Adam S Kibel
  • Agnieszka Dansonka-Mieszkowska
  • Agnieszka Michael
  • Aida K Dieffenbach
  • Aleksandra Gentry-Maharaj
  • Alice S Whittemore
  • Alicja Wolk
  • Alvaro Monteiro
  • Ana Peixoto
  • Andrzej Kierzek
  • Angela Cox
  • Anja Rudolph
  • Anna Gonzalez-Neira
  • Anna H Wu
  • Annika Lindblom
  • Anthony Swerdlow
  • Argyrios Ziogas
  • Arif B Ekici
  • Barbara Burwinkel
  • Beth Y Karlan
  • Nordestgaard, Børge
  • Carl Blomqvist
  • Catherine Phelan
  • Catriona McLean
  • Celeste Leigh Pearce
  • Celine Vachon
  • Cezary Cybulski
  • Chavdar Slavov
  • Christa Stegmaier
  • Christiane Maier
  • Christine B Ambrosone
  • Høgdall, Claus Kim
  • Craig C Teerlink
  • Daehee Kang
  • Daniel C Tessier
  • Daniel J Schaid
  • Daniel O Stram
  • Estrid Høgdall
  • Bojesen, Stig Egil
  • Kjær, Susanne Krüger
  • ABCTB Investigators

UNLABELLED: 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.

SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

Original languageEnglish
JournalCancer Discovery
Volume6
Issue number9
Pages (from-to)1052-67
Number of pages16
ISSN2159-8274
DOIs
Publication statusPublished - Sep 2016

    Research areas

  • Journal Article

ID: 167585371