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, Beesley, J, Al Olama, AA, Michailidou, K, Tyrer, J, Kote-Jarai, ZA, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ et al, 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, Hogdall, 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, Hogdall, 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, Lubinski, J, Stanford, JL, Bentez, 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, Matsuo, K, Muir, K, Offitt, K, Chen, K, Moysich, KB, Aittomaki, 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, Le, ND, Orr, N, Wentzensen, N, Pashayan, N, Peterlongo, P, Guenel, 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, SA, Berndt, S, Lee, SC, Teo, S-H, Thibodeau, SN, Bojesen, SE, Gapstur, SM, Kjaer, SK, Pejovic, T, Tammela, TLJ, Doerk, T, Bruening, 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 and Lambrechts, D (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). pp. 1052-1067.

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Abstract

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.

Item Type:	Article
Subjects :	Health Sciences
Divisions :	Faculty of Health and Medical Sciences > School of Health Sciences
Authors :	Name Email ORCID Kar, SP Beesley, J Al Olama, AA Michailidou, K Tyrer, J Kote-Jarai, ZA 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 Hogdall, 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 Hogdall, 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 Lubinski, J Stanford, JL Bentez, 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 Matsuo, K Muir, K Offitt, K Chen, K Moysich, KB Aittomaki, 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 Le, ND Orr, N Wentzensen, N Pashayan, N Peterlongo, P Guenel, 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, SA Berndt, S Lee, SC Teo, S-H Thibodeau, SN Bojesen, SE Gapstur, SM Kjaer, SK Pejovic, T Tammela, TLJ Doerk, T Bruening, 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
Date :	17 June 2016
DOI :	10.1158/2159-8290.CD-15-1227
Copyright Disclaimer :	©2016 AACR.
Uncontrolled Keywords :	Science & Technology, Life Sciences & Biomedicine, Oncology, TRAIL-INDUCED APOPTOSIS, PASSENGER COMPLEX CPC, BIOLOGICAL PATHWAYS, ENRICHMENT ANALYSIS, DEATH RECEPTORS, RISK LOCI, VARIANTS, CELLS, GENE, POPULATION
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	04 Apr 2017 17:08
Last Modified :	14 Jun 2018 13:20
URI:	http://epubs.surrey.ac.uk/id/eprint/813804

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