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

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Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. / 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; Nordestgaard, Børge G; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B; Høgdall, Claus K; Teerlink, Craig C; Kang, Daehee; Tessier, Daniel C; Schaid, Daniel J; Stram, Daniel O; Høgdall, Estrid; Bojesen, Stig E; Kjær, Susanne Krüger; ABCTB Investigators.

In: Cancer Discovery, Vol. 6, No. 9, 09.2016, p. 1052-67.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Kar, SP, Beesley, J, Amin Al Olama, A, Michailidou, K, Tyrer, J, Kote-Jarai, ZS, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ, Kibel, AS, Dansonka-Mieszkowska, A, Michael, A, Dieffenbach, AK, Gentry-Maharaj, A, Whittemore, AS, Wolk, A, Monteiro, A, Peixoto, A, Kierzek, A, Cox, A, Rudolph, A, Gonzalez-Neira, A, Wu, AH, Lindblom, A, Swerdlow, A, Ziogas, A, Ekici, AB, Burwinkel, B, Karlan, BY, Nordestgaard, BG, Blomqvist, C, Phelan, C, McLean, C, Pearce, CL, Vachon, C, Cybulski, C, Slavov, C, Stegmaier, C, Maier, C, Ambrosone, CB, Høgdall, CK, Teerlink, CC, Kang, D, Tessier, DC, Schaid, DJ, Stram, DO, Høgdall, E, Bojesen, SE, Kjær, SK & ABCTB Investigators 2016, 'Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types', Cancer Discovery, vol. 6, no. 9, pp. 1052-67. https://doi.org/10.1158/2159-8290.CD-15-1227

APA

Kar, S. P., Beesley, J., Amin Al Olama, A., Michailidou, K., Tyrer, J., Kote-Jarai, ZS., Lawrenson, K., Lindstrom, S., Ramus, S. J., Thompson, D. J., Kibel, A. S., Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A. K., Gentry-Maharaj, A., Whittemore, A. S., Wolk, A., Monteiro, A., Peixoto, A., ... ABCTB Investigators (2016). Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discovery, 6(9), 1052-67. https://doi.org/10.1158/2159-8290.CD-15-1227

Vancouver

Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai ZS et al. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discovery. 2016 Sep;6(9):1052-67. https://doi.org/10.1158/2159-8290.CD-15-1227

Author

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 ; Nordestgaard, Børge G ; Blomqvist, Carl ; Phelan, Catherine ; McLean, Catriona ; Pearce, Celeste Leigh ; Vachon, Celine ; Cybulski, Cezary ; Slavov, Chavdar ; Stegmaier, Christa ; Maier, Christiane ; Ambrosone, Christine B ; Høgdall, Claus K ; Teerlink, Craig C ; Kang, Daehee ; Tessier, Daniel C ; Schaid, Daniel J ; Stram, Daniel O ; Høgdall, Estrid ; Bojesen, Stig E ; Kjær, Susanne Krüger ; ABCTB Investigators. / Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. In: Cancer Discovery. 2016 ; Vol. 6, No. 9. pp. 1052-67.

Bibtex

@article{16b2fbd4663d45cb93d016a358e8a181,
title = "Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types",
abstract = "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. {\textcopyright}2016 AACR.This article is highlighted in the In This Issue feature, p. 932.",
keywords = "Journal Article",
author = "Kar, {Siddhartha P} and Jonathan Beesley and {Amin Al Olama}, Ali and Kyriaki Michailidou and Jonathan Tyrer and ZSofia Kote-Jarai and Kate Lawrenson and Sara Lindstrom and Ramus, {Susan J} and Thompson, {Deborah J} and Kibel, {Adam S} and Agnieszka Dansonka-Mieszkowska and Agnieszka Michael and Dieffenbach, {Aida K} and Aleksandra Gentry-Maharaj and Whittemore, {Alice S} and Alicja Wolk and Alvaro Monteiro and Ana Peixoto and Andrzej Kierzek and Angela Cox and Anja Rudolph and Anna Gonzalez-Neira and Wu, {Anna H} and Annika Lindblom and Anthony Swerdlow and Argyrios Ziogas and Ekici, {Arif B} and Barbara Burwinkel and Karlan, {Beth Y} and Nordestgaard, {B{\o}rge G} and Carl Blomqvist and Catherine Phelan and Catriona McLean and Pearce, {Celeste Leigh} and Celine Vachon and Cezary Cybulski and Chavdar Slavov and Christa Stegmaier and Christiane Maier and Ambrosone, {Christine B} and H{\o}gdall, {Claus K} and Teerlink, {Craig C} and Daehee Kang and Tessier, {Daniel C} and Schaid, {Daniel J} and Stram, {Daniel O} and Estrid H{\o}gdall and Bojesen, {Stig E} and Kj{\ae}r, {Susanne Kr{\"u}ger} and {ABCTB Investigators}",
note = "{\textcopyright}2016 American Association for Cancer Research.",
year = "2016",
month = sep,
doi = "10.1158/2159-8290.CD-15-1227",
language = "English",
volume = "6",
pages = "1052--67",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research",
number = "9",

}

RIS

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

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

VL - 6

SP - 1052

EP - 1067

JO - Cancer Discovery

JF - Cancer Discovery

SN - 2159-8274

IS - 9

ER -

ID: 167585371