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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, 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 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 :
NameEmailORCID
Kar, SPUNSPECIFIEDUNSPECIFIED
Beesley, JUNSPECIFIEDUNSPECIFIED
Al Olama, AAUNSPECIFIEDUNSPECIFIED
Michailidou, KUNSPECIFIEDUNSPECIFIED
Tyrer, JUNSPECIFIEDUNSPECIFIED
Kote-Jarai, ZAUNSPECIFIEDUNSPECIFIED
Lawrenson, KUNSPECIFIEDUNSPECIFIED
Lindstrom, SUNSPECIFIEDUNSPECIFIED
Ramus, SJUNSPECIFIEDUNSPECIFIED
Thompson, DJUNSPECIFIEDUNSPECIFIED
Kibel, ASUNSPECIFIEDUNSPECIFIED
Dansonka-Mieszkowska, AUNSPECIFIEDUNSPECIFIED
Michael, AUNSPECIFIEDUNSPECIFIED
Dieffenbach, AKUNSPECIFIEDUNSPECIFIED
Gentry-Maharaj, AUNSPECIFIEDUNSPECIFIED
Whittemore, ASUNSPECIFIEDUNSPECIFIED
Wolk, AUNSPECIFIEDUNSPECIFIED
Monteiro, AUNSPECIFIEDUNSPECIFIED
Peixoto, AUNSPECIFIEDUNSPECIFIED
Kierzek, AUNSPECIFIEDUNSPECIFIED
Cox, AUNSPECIFIEDUNSPECIFIED
Rudolph, AUNSPECIFIEDUNSPECIFIED
Gonzalez-Neira, AUNSPECIFIEDUNSPECIFIED
Wu, AHUNSPECIFIEDUNSPECIFIED
Lindblom, AUNSPECIFIEDUNSPECIFIED
Swerdlow, AUNSPECIFIEDUNSPECIFIED
Ziogas, AUNSPECIFIEDUNSPECIFIED
Ekici, ABUNSPECIFIEDUNSPECIFIED
Burwinkel, BUNSPECIFIEDUNSPECIFIED
Karlan, BYUNSPECIFIEDUNSPECIFIED
Nordestgaard, BGUNSPECIFIEDUNSPECIFIED
Blomqvist, CUNSPECIFIEDUNSPECIFIED
Phelan, CUNSPECIFIEDUNSPECIFIED
McLean, CUNSPECIFIEDUNSPECIFIED
Pearce, CLUNSPECIFIEDUNSPECIFIED
Vachon, CUNSPECIFIEDUNSPECIFIED
Cybulski, CUNSPECIFIEDUNSPECIFIED
Slavov, CUNSPECIFIEDUNSPECIFIED
Stegmaier, CUNSPECIFIEDUNSPECIFIED
Maier, CUNSPECIFIEDUNSPECIFIED
Ambrosone, CBUNSPECIFIEDUNSPECIFIED
Hogdall, CKUNSPECIFIEDUNSPECIFIED
Teerlink, CCUNSPECIFIEDUNSPECIFIED
Kang, DUNSPECIFIEDUNSPECIFIED
Tessier, DCUNSPECIFIEDUNSPECIFIED
Schaid, DJUNSPECIFIEDUNSPECIFIED
Stram, DOUNSPECIFIEDUNSPECIFIED
Cramer, DWUNSPECIFIEDUNSPECIFIED
Neal, DEUNSPECIFIEDUNSPECIFIED
Eccles, DUNSPECIFIEDUNSPECIFIED
Flesch-Janys, DUNSPECIFIEDUNSPECIFIED
Edwards, DRVUNSPECIFIEDUNSPECIFIED
Wokozorczyk, DUNSPECIFIEDUNSPECIFIED
Levine, DAUNSPECIFIEDUNSPECIFIED
Yannoukakos, DUNSPECIFIEDUNSPECIFIED
Sawyer, EJUNSPECIFIEDUNSPECIFIED
Bandera, EVUNSPECIFIEDUNSPECIFIED
Poole, EMUNSPECIFIEDUNSPECIFIED
Goode, ELUNSPECIFIEDUNSPECIFIED
Khusnutdinova, EUNSPECIFIEDUNSPECIFIED
Hogdall, EUNSPECIFIEDUNSPECIFIED
Song, FUNSPECIFIEDUNSPECIFIED
Bruinsma, FUNSPECIFIEDUNSPECIFIED
Heitz, FUNSPECIFIEDUNSPECIFIED
Modugno, FUNSPECIFIEDUNSPECIFIED
Hamdy, FCUNSPECIFIEDUNSPECIFIED
Wiklund, FUNSPECIFIEDUNSPECIFIED
Giles, GGUNSPECIFIEDUNSPECIFIED
Olsson, HUNSPECIFIEDUNSPECIFIED
Wildiers, HUNSPECIFIEDUNSPECIFIED
Ulmer, H-UUNSPECIFIEDUNSPECIFIED
Pandha, HUNSPECIFIEDUNSPECIFIED
Risch, HAUNSPECIFIEDUNSPECIFIED
Darabi, HUNSPECIFIEDUNSPECIFIED
Salvesen, HBUNSPECIFIEDUNSPECIFIED
Nevanlinna, HUNSPECIFIEDUNSPECIFIED
Gronberg, HUNSPECIFIEDUNSPECIFIED
Brenner, HUNSPECIFIEDUNSPECIFIED
Brauch, HUNSPECIFIEDUNSPECIFIED
Anton-Culver, HUNSPECIFIEDUNSPECIFIED
Song, HUNSPECIFIEDUNSPECIFIED
Lim, H-YUNSPECIFIEDUNSPECIFIED
McNeish, IUNSPECIFIEDUNSPECIFIED
Campbell, IUNSPECIFIEDUNSPECIFIED
Vergote, IUNSPECIFIEDUNSPECIFIED
Gronwald, JUNSPECIFIEDUNSPECIFIED
Lubinski, JUNSPECIFIEDUNSPECIFIED
Stanford, JLUNSPECIFIEDUNSPECIFIED
Bentez, JUNSPECIFIEDUNSPECIFIED
Doherty, JAUNSPECIFIEDUNSPECIFIED
Permuth, JBUNSPECIFIEDUNSPECIFIED
Chang-Claude, JUNSPECIFIEDUNSPECIFIED
Donovan, JLUNSPECIFIEDUNSPECIFIED
Dennis, JUNSPECIFIEDUNSPECIFIED
Schildkraut, JMUNSPECIFIEDUNSPECIFIED
Schleutker, JUNSPECIFIEDUNSPECIFIED
Hopper, JLUNSPECIFIEDUNSPECIFIED
Kupryjanczyk, JUNSPECIFIEDUNSPECIFIED
Park, JYUNSPECIFIEDUNSPECIFIED
Figueroa, JUNSPECIFIEDUNSPECIFIED
Clements, JAUNSPECIFIEDUNSPECIFIED
Knight, JAUNSPECIFIEDUNSPECIFIED
Peto, JUNSPECIFIEDUNSPECIFIED
Cunningham, JMUNSPECIFIEDUNSPECIFIED
Pow-Sang, JUNSPECIFIEDUNSPECIFIED
Batra, JUNSPECIFIEDUNSPECIFIED
Czene, KUNSPECIFIEDUNSPECIFIED
Lu, KHUNSPECIFIEDUNSPECIFIED
Herkommer, KUNSPECIFIEDUNSPECIFIED
Khaw, K-TUNSPECIFIEDUNSPECIFIED
Matsuo, KUNSPECIFIEDUNSPECIFIED
Muir, KUNSPECIFIEDUNSPECIFIED
Offitt, KUNSPECIFIEDUNSPECIFIED
Chen, KUNSPECIFIEDUNSPECIFIED
Moysich, KBUNSPECIFIEDUNSPECIFIED
Aittomaki, KUNSPECIFIEDUNSPECIFIED
Odunsi, KUNSPECIFIEDUNSPECIFIED
Kiemeney, LAUNSPECIFIEDUNSPECIFIED
Massuger, LFAGUNSPECIFIEDUNSPECIFIED
Fitzgerald, LMUNSPECIFIEDUNSPECIFIED
Cook, LSUNSPECIFIEDUNSPECIFIED
Cannon-Albright, LUNSPECIFIEDUNSPECIFIED
Hooning, MJUNSPECIFIEDUNSPECIFIED
Pike, MCUNSPECIFIEDUNSPECIFIED
Bolla, MKUNSPECIFIEDUNSPECIFIED
Luedeke, MUNSPECIFIEDUNSPECIFIED
Teixeira, MRUNSPECIFIEDUNSPECIFIED
Goodman, MTUNSPECIFIEDUNSPECIFIED
Schmidt, MKUNSPECIFIEDUNSPECIFIED
Riggan, MUNSPECIFIEDUNSPECIFIED
Aly, MUNSPECIFIEDUNSPECIFIED
Rossing, MAUNSPECIFIEDUNSPECIFIED
Beckmann, MWUNSPECIFIEDUNSPECIFIED
Moisse, MUNSPECIFIEDUNSPECIFIED
Sanderson, MUNSPECIFIEDUNSPECIFIED
Southey, MCUNSPECIFIEDUNSPECIFIED
Jones, MUNSPECIFIEDUNSPECIFIED
Lush, MUNSPECIFIEDUNSPECIFIED
Hildebrandt, MATUNSPECIFIEDUNSPECIFIED
Hou, M-FUNSPECIFIEDUNSPECIFIED
Schoemaker, MJUNSPECIFIEDUNSPECIFIED
Garcia-Closas, MUNSPECIFIEDUNSPECIFIED
Bogdanova, NUNSPECIFIEDUNSPECIFIED
Rahman, NUNSPECIFIEDUNSPECIFIED
Le, NDUNSPECIFIEDUNSPECIFIED
Orr, NUNSPECIFIEDUNSPECIFIED
Wentzensen, NUNSPECIFIEDUNSPECIFIED
Pashayan, NUNSPECIFIEDUNSPECIFIED
Peterlongo, PUNSPECIFIEDUNSPECIFIED
Guenel, PUNSPECIFIEDUNSPECIFIED
Brennan, PUNSPECIFIEDUNSPECIFIED
Paulo, PUNSPECIFIEDUNSPECIFIED
Webb, PMUNSPECIFIEDUNSPECIFIED
Broberg, PUNSPECIFIEDUNSPECIFIED
Fasching, PAUNSPECIFIEDUNSPECIFIED
Devilee, PUNSPECIFIEDUNSPECIFIED
Wang, QUNSPECIFIEDUNSPECIFIED
Cai, QUNSPECIFIEDUNSPECIFIED
Li, QUNSPECIFIEDUNSPECIFIED
Kaneva, RUNSPECIFIEDUNSPECIFIED
Butzow, RUNSPECIFIEDUNSPECIFIED
Kopperud, RKUNSPECIFIEDUNSPECIFIED
Schmutzler, RKUNSPECIFIEDUNSPECIFIED
Stephenson, RAUNSPECIFIEDUNSPECIFIED
MacInnis, RJUNSPECIFIEDUNSPECIFIED
Hoover, RNUNSPECIFIEDUNSPECIFIED
Winqvist, RUNSPECIFIEDUNSPECIFIED
Ness, RUNSPECIFIEDUNSPECIFIED
Milne, RLUNSPECIFIEDUNSPECIFIED
Travis, RCUNSPECIFIEDUNSPECIFIED
Benlloch, SUNSPECIFIEDUNSPECIFIED
Olson, SHUNSPECIFIEDUNSPECIFIED
McDonnell, SKUNSPECIFIEDUNSPECIFIED
Tworoger, SSUNSPECIFIEDUNSPECIFIED
Maia, SAUNSPECIFIEDUNSPECIFIED
Berndt, SUNSPECIFIEDUNSPECIFIED
Lee, SCUNSPECIFIEDUNSPECIFIED
Teo, S-HUNSPECIFIEDUNSPECIFIED
Thibodeau, SNUNSPECIFIEDUNSPECIFIED
Bojesen, SEUNSPECIFIEDUNSPECIFIED
Gapstur, SMUNSPECIFIEDUNSPECIFIED
Kjaer, SKUNSPECIFIEDUNSPECIFIED
Pejovic, TUNSPECIFIEDUNSPECIFIED
Tammela, TLJUNSPECIFIEDUNSPECIFIED
Doerk, TUNSPECIFIEDUNSPECIFIED
Bruening, TUNSPECIFIEDUNSPECIFIED
Wahlfors, TUNSPECIFIEDUNSPECIFIED
Key, TJUNSPECIFIEDUNSPECIFIED
Edwards, TLUNSPECIFIEDUNSPECIFIED
Menon, UUNSPECIFIEDUNSPECIFIED
Hamann, UUNSPECIFIEDUNSPECIFIED
Mitev, VUNSPECIFIEDUNSPECIFIED
Kosma, V-MUNSPECIFIEDUNSPECIFIED
Setiawan, VWUNSPECIFIEDUNSPECIFIED
Kristensen, VUNSPECIFIEDUNSPECIFIED
Arndt, VUNSPECIFIEDUNSPECIFIED
Vogel, WUNSPECIFIEDUNSPECIFIED
Zheng, WUNSPECIFIEDUNSPECIFIED
Sieh, WUNSPECIFIEDUNSPECIFIED
Blot, WJUNSPECIFIEDUNSPECIFIED
Kluzniak, WUNSPECIFIEDUNSPECIFIED
Shu, X-OUNSPECIFIEDUNSPECIFIED
Gao, Y-TUNSPECIFIEDUNSPECIFIED
Schumacher, FUNSPECIFIEDUNSPECIFIED
Freedman, MLUNSPECIFIEDUNSPECIFIED
Berchuck, AUNSPECIFIEDUNSPECIFIED
Dunning, AMUNSPECIFIEDUNSPECIFIED
Simard, JUNSPECIFIEDUNSPECIFIED
Haiman, CAUNSPECIFIEDUNSPECIFIED
Spurdle, AUNSPECIFIEDUNSPECIFIED
Sellers, TAUNSPECIFIEDUNSPECIFIED
Hunter, DJUNSPECIFIEDUNSPECIFIED
Henderson, BEUNSPECIFIEDUNSPECIFIED
Kraft, PUNSPECIFIEDUNSPECIFIED
Chanock, SJUNSPECIFIEDUNSPECIFIED
Couch, FJUNSPECIFIEDUNSPECIFIED
Hall, PUNSPECIFIEDUNSPECIFIED
Gayther, SAUNSPECIFIEDUNSPECIFIED
Easton, DFUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GUNSPECIFIEDUNSPECIFIED
Eeles, RUNSPECIFIEDUNSPECIFIED
Pharoah, PDPUNSPECIFIEDUNSPECIFIED
Lambrechts, DUNSPECIFIEDUNSPECIFIED
Date : 1 September 2016
Identification Number : 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 :
Depositing User : Symplectic Elements
Date Deposited : 04 Apr 2017 17:08
Last Modified : 02 Sep 2017 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/813804

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