TY - JOUR
T1 - Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
AU - Kar, Siddhartha P
AU - Beesley, Jonathan
AU - Amin Al Olama, Ali
AU - Michailidou, Kyriaki
AU - Tyrer, Jonathan
AU - Kote-Jarai, ZSofia
AU - Lawrenson, Kate
AU - Lindstrom, Sara
AU - Ramus, Susan J
AU - Thompson, Deborah J
AU - Kibel, Adam S
AU - Dansonka-Mieszkowska, Agnieszka
AU - Michael, Agnieszka
AU - Dieffenbach, Aida K
AU - Gentry-Maharaj, Aleksandra
AU - Whittemore, Alice S
AU - Wolk, Alicja
AU - Monteiro, Alvaro
AU - Peixoto, Ana
AU - Kierzek, Andrzej
AU - Cox, Angela
AU - Rudolph, Anja
AU - Gonzalez-Neira, Anna
AU - Wu, Anna H
AU - Lindblom, Annika
AU - Swerdlow, Anthony
AU - Ziogas, Argyrios
AU - Ekici, Arif B
AU - Burwinkel, Barbara
AU - Karlan, Beth Y
AU - Nordestgaard, Børge G
AU - Blomqvist, Carl
AU - Phelan, Catherine
AU - McLean, Catriona
AU - Pearce, Celeste Leigh
AU - Vachon, Celine
AU - Cybulski, Cezary
AU - Slavov, Chavdar
AU - Stegmaier, Christa
AU - Maier, Christiane
AU - Ambrosone, Christine B
AU - Høgdall, Claus K
AU - Teerlink, Craig C
AU - Kang, Daehee
AU - Tessier, Daniel C
AU - Schaid, Daniel J
AU - Stram, Daniel O
AU - Høgdall, Estrid Vilma Solyom
AU - Bojesen, Stig E
AU - Kjær, Susanne Krüger
AU - ABCTB Investigators
N1 - ©2016 American Association for Cancer Research.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1158/2159-8290.CD-15-1227
DO - 10.1158/2159-8290.CD-15-1227
M3 - Journal article
C2 - 27432226
SN - 2159-8274
VL - 6
SP - 1052
EP - 1067
JO - Cancer Discovery
JF - Cancer Discovery
IS - 9
ER -