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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, SP and Beesley, J and Amin Al Olama, A and Michailidou, K and Tyrer, J and Kote-Jarai, Z and Lawrenson, K and Lindstrom, S and Ramus, SJ and Thompson, DJ and Kibel, AS and Dansonka-Mieszkowska, A and Michael, A and Dieffenbach, AK and Gentry-Maharaj, A and Whittemore, AS and Wolk, A and Monteiro, A and Peixoto, A and Kierzek, A and Cox, A and Rudolph, A and Gonzalez-Neira, A and Wu, AH and Lindblom, A and Swerdlow, A and Ziogas, A and Ekici, AB and Burwinkel, B and Karlan, BY and Nordestgaard, BG and Blomqvist, C and Phelan, C and McLean, C and Pearce, CL and Vachon, C and Cybulski, C and Slavov, C and Stegmaier, C and Maier, C and Ambrosone, CB and Hogdall, CK and Teerlink, CC and Kang, D and Tessier, DC and Schaid, DJ and Stram, DO and Cramer, DW and Neal, DE and Eccles, D and Flesch-Janys, D and Velez Edwards, DR and Wokozorczyk, D and Levine, DA and Yannoukakos, D and Sawyer, EJ and Bandera, EV and Poole, EM and Goode, EL and Khusnutdinova, E and Hogdall, E and Song, F and Bruinsma, F and Heitz, F and Modugno, F and Hamdy, FC and Wiklund, F and Giles, GG and Olsson, H and Wildiers, H and Ulmer, H-U and Pandha, H and Risch, HA and Darabi, H and Salvesen, HB and Nevanlinna, H and Gronberg, H and Brenner, H and Brauch, H and Anton-Culver, H and Song, H and Lim, H-Y and McNeish, I and Campbell, I and Vergote, I and Gronwald, J and Lubinski, J and Stanford, JL and Benitez, J and Doherty, JA and Permuth, JB and Chang-Claude, J and Donovan, JL and Dennis, J and Schildkraut, JM and Schleutker, J and Hopper, JL and Kupryjanczyk, J and Park, JY and Figueroa, J and Clements, JA and Knight, JA and Peto, J and Cunningham, JM and Pow-Sang, J and Batra, J and Czene, K and Lu, KH and Herkommer, K and Khaw, K-T and Matsuo, K and Muir, K and Offitt, K and Chen, K and Moysich, KB and Aittomaki, K and Odunsi, K and Kiemeney, LA and Massuger, LFAG and Fitzgerald, LM and Cook, LS and Cannon-Albright, L and Hooning, MJ and Pike, MC and Bolla, MK and Luedeke, M and Teixeira, MR and Goodman, MT and Schmidt, MK and Riggan, M and Aly, M and Rossing, MA and Beckmann, MW and Moisse, M and Sanderson, M and Southey, MC and Jones, M and Lush, M and Hildebrandt, MAT and Hou, M-F and Schoemaker, MJ and Garcia-Closas, M and Bogdanova, N and Rahman, N and Le, ND and Orr, N and Wentzensen, N and Pashayan, N and Peterlongo, P and Guenel, P and Brennan, P and Paulo, P and Webb, PM and Broberg, P and Fasching, PA and Devilee, P and Wang, Q and Cai, Q and Li, Q and Kaneva, R and Butzow, R and Kopperud, RK and Schmutzler, RK and Stephenson, RA and MacInnis, RJ and Hoover, RN and Winqvis, R and Ness, R and Milne, RL and Travis, RC and Benlloch, S and Olson, SH and McDonnell, SK and Tworoger, SS and Maia, S and Berndt, S and Lee, SC and Teo, S-H and Thibodeau, SN and Bojesen, SE and Gapstur, SM and Kjaer, SK and Pejovic, T and Tammela, TLJ and Dork, TT and Bruning, T and Wahlfors, T and Key, TJ and Edwards, TL and Menon, U and Hamann, U and Mitev, V and Kosma, V-M and Setiawan, VW and Kristensen, V and Arndt, V and Vogel, W and Zheng, W and Sieh, W and Blot, WJ and Kluzniak, W and Shu, X-O and Gao, Y-G and Schumacher, F and Freedman, ML and Berchuck, A and Dunning, AM and Simard, J and Haiman, CA and Spurdle, A and Sellers, TA and Hunter, DJ and Henderson, BE and Kraft, P and Chanock, SJ and Couch, FJ and Hall, P and Gayther, SA and Easton, DF and Chenevix-Trench, G and Eeles, R and Pharoah, PDP and Lambrechts, D, ABCTB Investigators, AOCS Study Grp Australian Canc, APCB BioResource, KConFab Investigators, NBCS Investigators, GENICA Network, PRACTICAL Consortium, 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) pp. 1053-1067. ISSN 2159-8274 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 AACR

DOI: doi:10.1158/2159-8290.CD-15-1227


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.

Strong>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.

Item Details

Item Type:Refereed Article
Keywords:meta-analysis, breast, prostate, ovarian, cancer
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer genetics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Fitzgerald, LM (Dr Liesel FitzGerald)
ID Code:110623
Year Published:2016
Web of Science® Times Cited:113
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-05
Last Modified:2022-08-23

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