Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
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Authors
Kar, SP
Beesley, J
Amin Al Olama, A
Michailidou, K
Tyrer, J
Kote-Jarai, Z
Lawrenson, K
Lindstrom, S
Ramus, SJ
Thompson, DJ
ABCTB Investigators,
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
AOCS Study Group & Australian Cancer Study (Ovarian Cancer),
APCB BioResource,
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
Cramer, DW
Neal, DE
Eccles, D
Flesch-Janys, D
Edwards, DRV
Wokozorczyk, D
Levine, DA
Yannoukakos, D
Sawyer, EJ
Bandera, EV
Poole, EM
Goode, EL
Khusnutdinova, E
Høgdall, E
Song, F
Bruinsma, F
Heitz, F
Modugno, F
Hamdy, FC
Wiklund, F
Giles, GG
Olsson, H
Wildiers, H
Ulmer, H-U
Pandha, H
Risch, HA
Darabi, H
Salvesen, HB
Nevanlinna, H
Gronberg, H
Brenner, H
Brauch, H
Anton-Culver, H
Song, H
Lim, H-Y
McNeish, I
Campbell, I
Vergote, I
Gronwald, J
Lubiński, J
Stanford, JL
Benítez, J
Doherty, JA
Permuth, JB
Chang-Claude, J
Donovan, JL
Dennis, J
Schildkraut, JM
Schleutker, J
Hopper, JL
Kupryjanczyk, J
Park, JY
Figueroa, J
Clements, JA
Knight, JA
Peto, J
Cunningham, JM
Pow-Sang, J
Batra, J
Czene, K
Lu, KH
Herkommer, K
Khaw, K-T
kConFab Investigators,
Matsuo, K
Muir, K
Offitt, K
Chen, K
Moysich, KB
Aittomäki, K
Odunsi, K
Kiemeney, LA
Massuger, LFAG
Fitzgerald, LM
Cook, LS
Cannon-Albright, L
Hooning, MJ
Pike, MC
Bolla, MK
Luedeke, M
Teixeira, MR
Goodman, MT
Schmidt, MK
Riggan, M
Aly, M
Rossing, MA
Beckmann, MW
Moisse, M
Sanderson, M
Southey, MC
Jones, M
Lush, M
Hildebrandt, MAT
Hou, M-F
Schoemaker, MJ
Garcia-Closas, M
Bogdanova, N
Rahman, N
NBCS Investigators,
Le, ND
Orr, N
Wentzensen, N
Pashayan, N
Peterlongo, P
Guénel, P
Brennan, P
Paulo, P
Webb, PM
Broberg, P
Fasching, PA
Devilee, P
Wang, Q
Cai, Q
Li, Q
Kaneva, R
Butzow, R
Kopperud, RK
Schmutzler, RK
Stephenson, RA
MacInnis, RJ
Hoover, RN
Winqvist, R
Ness, R
Milne, RL
Travis, RC
Benlloch, S
Olson, SH
McDonnell, SK
Tworoger, SS
Maia, S
Berndt, S
Lee, SC
Teo, S-H
Thibodeau, SN
Bojesen, SE
Gapstur, SM
Kjær, SK
Pejovic, T
Tammela, TLJ
GENICA Network,
PRACTICAL consortium,
Dörk, T
Brüning, T
Wahlfors, T
Key, TJ
Edwards, TL
Menon, U
Hamann, U
Mitev, V
Kosma, V-M
Setiawan, VW
Kristensen, V
Arndt, V
Vogel, W
Zheng, W
Sieh, W
Blot, WJ
Kluzniak, W
Shu, X-O
Gao, Y-T
Schumacher, F
Freedman, ML
Berchuck, A
Dunning, AM
Simard, J
Haiman, CA
Spurdle, A
Sellers, TA
Hunter, DJ
Henderson, BE
Kraft, P
Chanock, SJ
Couch, FJ
Hall, P
Gayther, SA
Easton, DF
Chenevix-Trench, G
Eeles, R
Pharoah, PDP
Lambrechts, D
Beesley, J
Amin Al Olama, A
Michailidou, K
Tyrer, J
Kote-Jarai, Z
Lawrenson, K
Lindstrom, S
Ramus, SJ
Thompson, DJ
ABCTB Investigators,
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
AOCS Study Group & Australian Cancer Study (Ovarian Cancer),
APCB BioResource,
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
Cramer, DW
Neal, DE
Eccles, D
Flesch-Janys, D
Edwards, DRV
Wokozorczyk, D
Levine, DA
Yannoukakos, D
Sawyer, EJ
Bandera, EV
Poole, EM
Goode, EL
Khusnutdinova, E
Høgdall, E
Song, F
Bruinsma, F
Heitz, F
Modugno, F
Hamdy, FC
Wiklund, F
Giles, GG
Olsson, H
Wildiers, H
Ulmer, H-U
Pandha, H
Risch, HA
Darabi, H
Salvesen, HB
Nevanlinna, H
Gronberg, H
Brenner, H
Brauch, H
Anton-Culver, H
Song, H
Lim, H-Y
McNeish, I
Campbell, I
Vergote, I
Gronwald, J
Lubiński, J
Stanford, JL
Benítez, J
Doherty, JA
Permuth, JB
Chang-Claude, J
Donovan, JL
Dennis, J
Schildkraut, JM
Schleutker, J
Hopper, JL
Kupryjanczyk, J
Park, JY
Figueroa, J
Clements, JA
Knight, JA
Peto, J
Cunningham, JM
Pow-Sang, J
Batra, J
Czene, K
Lu, KH
Herkommer, K
Khaw, K-T
kConFab Investigators,
Matsuo, K
Muir, K
Offitt, K
Chen, K
Moysich, KB
Aittomäki, K
Odunsi, K
Kiemeney, LA
Massuger, LFAG
Fitzgerald, LM
Cook, LS
Cannon-Albright, L
Hooning, MJ
Pike, MC
Bolla, MK
Luedeke, M
Teixeira, MR
Goodman, MT
Schmidt, MK
Riggan, M
Aly, M
Rossing, MA
Beckmann, MW
Moisse, M
Sanderson, M
Southey, MC
Jones, M
Lush, M
Hildebrandt, MAT
Hou, M-F
Schoemaker, MJ
Garcia-Closas, M
Bogdanova, N
Rahman, N
NBCS Investigators,
Le, ND
Orr, N
Wentzensen, N
Pashayan, N
Peterlongo, P
Guénel, P
Brennan, P
Paulo, P
Webb, PM
Broberg, P
Fasching, PA
Devilee, P
Wang, Q
Cai, Q
Li, Q
Kaneva, R
Butzow, R
Kopperud, RK
Schmutzler, RK
Stephenson, RA
MacInnis, RJ
Hoover, RN
Winqvist, R
Ness, R
Milne, RL
Travis, RC
Benlloch, S
Olson, SH
McDonnell, SK
Tworoger, SS
Maia, S
Berndt, S
Lee, SC
Teo, S-H
Thibodeau, SN
Bojesen, SE
Gapstur, SM
Kjær, SK
Pejovic, T
Tammela, TLJ
GENICA Network,
PRACTICAL consortium,
Dörk, T
Brüning, T
Wahlfors, T
Key, TJ
Edwards, TL
Menon, U
Hamann, U
Mitev, V
Kosma, V-M
Setiawan, VW
Kristensen, V
Arndt, V
Vogel, W
Zheng, W
Sieh, W
Blot, WJ
Kluzniak, W
Shu, X-O
Gao, Y-T
Schumacher, F
Freedman, ML
Berchuck, A
Dunning, AM
Simard, J
Haiman, CA
Spurdle, A
Sellers, TA
Hunter, DJ
Henderson, BE
Kraft, P
Chanock, SJ
Couch, FJ
Hall, P
Gayther, SA
Easton, DF
Chenevix-Trench, G
Eeles, R
Pharoah, PDP
Lambrechts, D
Document Type
Journal Article
Date
2016-09-01
Date Accepted
2016-06-07
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. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
Citation
Cancer discovery, 2016, 6 (9), pp. 1052 - 1067
Rights
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
2159-8274
eISSN
2159-8290
Research Team
Complex Trait Genetics
Aetiological Epidemiology
Genetic Susceptibility
Oncogenetics
Aetiological Epidemiology
Genetic Susceptibility
Oncogenetics