Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types

Article, Other literature type English OPEN
Kar, Siddhartha P. ; Beesley, Jonathan ; Amin Al Olama, Ali ; Michailidou, Kyriaki ; Tyrer, Jonathan ; Kote-Jarai, ZSofia ; Lawrenson, Kate ; Lindstrom, Sara ; Ramus, Susan J. ; Thompson, Deborah J. ; Kibel, Adam S. ; Dansonka-Mieszkowska, Agnieszka ; Michael, Agnieszka ; Dieffenbach, Aida K. ; Gentry-Maharaj, Aleksandra ; Whittemore, Alice S. ; Wolk, Alicja ; Monteiro, Alvaro ; Peixoto, Ana ; Kierzek, Andrzej ; Cox, Angela ; Rudolph, Anja ; Gonzalez-Neira, Anna ; Wu, Anna H. ; Lindblom, Annika ; Swerdlow, Anthony ; Ziogas, Argyrios ; Ekici, Arif B. ; Burwinkel, Barbara ; Karlan, Beth Y. ... view all 223 authors (2016)
  • Publisher: American Association for Cancer Research
  • Related identifiers: doi: 10.1158/2159-8290.CD-15-1227
  • Subject: /dk/atira/pure/researchoutput/pubmedpublicationtype/D013486 | /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428 | /dk/atira/pure/researchoutput/pubmedpublicationtype/D013485 | ovarian cancer | breast cancer | pleiotropy | /dk/atira/pure/researchoutput/pubmedpublicationtype/D052061 | Article | Research Support, Non-U.S. Gov't | prostate cancer | Research Support, N.I.H., Extramural | Research Support, U.S. Gov't, Non-P.H.S. | Journal Article | genome-wide association studies

<p>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 &lt; 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 &lt; 10(-5) in the three-cancer meta-analysis.</p><p>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); 1-16. ©2016 AACR.</p>