Person: Kibel, Adam
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Publication Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
(American Association for Cancer Research (AACR), 2016) Kar, S. P.; Beesley, J.; Amin Al Olama, A.; Michailidou, K.; Tyrer, J.; Kote-Jarai, Z.; Lawrenson, K.; Lindstrom, S.; Ramus, S. J.; Thompson, D. J.; Kibel, Adam; Dansonka-Mieszkowska, A.; Michael, A.; Dieffenbach, A. K.; Gentry-Maharaj, A.; Whittemore, A. S.; Wolk, A.; Monteiro, A.; Peixoto, A.; Kierzek, A.; Cox, A.; Rudolph, A.; Gonzalez-Neira, A.; Wu, A. H.; Lindblom, A.; Swerdlow, A.; Ziogas, A.; Ekici, A. B.; Burwinkel, B.; Karlan, B. Y.; Nordestgaard, B. G.; Blomqvist, C.; Phelan, C.; McLean, C.; Pearce, C. L.; Vachon, C.; Cybulski, C.; Slavov, C.; Stegmaier, C.; Maier, C.; Ambrosone, C. B.; Hogdall, C. K.; Teerlink, C. C.; Kang, D.; Tessier, D. C.; Schaid, D. J.; Stram, D. O.; Cramer, Daniel; Neal, D. E.; Eccles, D.; Flesch-Janys, D.; Edwards, D. R. V.; Wokozorczyk, D.; Levine, D. A.; Yannoukakos, D.; Sawyer, E. J.; Bandera, E. V.; Poole, Elizabeth M.; Goode, E. L.; Khusnutdinova, E.; Hogdall, E.; Song, F; Bruinsma, F.; Heitz, F.; Modugno, F.; Hamdy, F. C.; Wiklund, F.; Giles, G. G.; Olsson, H.; Wildiers, H.; Ulmer, H.-U.; Pandha, H.; Risch, H. A.; Darabi, H.; Salvesen, H. B.; 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, J. L.; Benitez, J.; Doherty, J. A.; Permuth, J. B.; Chang-Claude, J.; Donovan, J. L.; Dennis, J.; Schildkraut, J. M.; Schleutker, J.; Hopper, J. L.; Kupryjanczyk, J.; Park, J. Y.; Figueroa, J.; Clements, J. A.; Knight, J. A.; Peto, J.; Cunningham, J. M.; Pow-Sang, J.; Batra, J.; Czene, K.; Lu, K. H.; Herkommer, K.; Khaw, K.-T.; Matsuo, K.; Muir, K.; Offitt, K.; Chen, K.; Moysich, K. B.; Aittoma ki, K.; Odunsi, K.; Kiemeney, L. A.; Massuger, L. F. A. G.; Fitzgerald, L. M.; Cook, L. S.; Cannon-Albright, L.; Hooning, M. J.; Pike, M. C.; Bolla, M. K.; Luedeke, M.; Teixeira, M. R.; Goodman, M. T.; Schmidt, M. K.; Riggan, M.; Aly, M.; Rossing, M. A.; Beckmann, M. W.; Moisse, M.; Sanderson, M.; Southey, M. C.; Jones, M.; Lush, M.; Hildebrandt, M. A. T.; Hou, M.-F.; Schoemaker, M. J.; Garcia-Closas, M.; Bogdanova, N.; Rahman, N.; Le, N. D.; Orr, N.; Wentzensen, N.; Pashayan, N.; Peterlongo, P.; Guenel, P.; Brennan, P.; Paulo, P.; Webb, P. M.; Broberg, P.; Fasching, P. A.; Devilee, P.; Wang, Q.; Cai, Q.; Li, Q.; Kaneva, R.; Butzow, R.; Kopperud, R. K.; Schmutzler, R. K.; Stephenson, R. A.; MacInnis, R. J.; Hoover, R. N.; Winqvist, R.; Ness, R.; Milne, R. L.; Travis, R. C.; Benlloch, S.; Olson, S. H.; McDonnell, S. K.; Tworoger, Shelley; Maia, S.; Berndt, S.; Lee, S. C.; Teo, S.-H.; Thibodeau, S. N.; Bojesen, S. E.; Gapstur, S. M.; Kjaer, S. K.; Pejovic, T.; Tammela, T. L. J.; Do rk, T.; Bru ning, T.; Wahlfors, T.; Key, T. J.; Edwards, T. L.; Menon, U.; Hamann, U.; Mitev, V.; Kosma, V.-M.; Setiawan, V. W.; Kristensen, V.; Arndt, V.; Vogel, W.; Zheng, W.; Sieh, W.; Blot, W. J.; Kluzniak, W.; Shu, X.-O.; Gao, Y.-T.; Schumacher, F.; Freedman, M. L.; Berchuck, A.; Dunning, A. M.; Simard, J.; Haiman, C. A.; Spurdle, A.; Sellers, T. A.; Hunter, David; Henderson, B. E.; Kraft, Peter; Chanock, S. J.; Couch, F. J.; Hall, P.; Gayther, S. A.; Easton, D. F.; Chenevix-Trench, G.; Eeles, R.; Pharoah, P. D. P.; Lambrechts, D.; undefined, undefinedBreast, 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.
Publication PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
(2016) Southey, Melissa C; Goldgar, David E; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L; Dörk, Thilo; Claes, Kathleen BM; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A; Dowty, James G; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Yang, Rongxi; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan; Ziogas, Argyrios; Clarke, Christina A; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Antonenkova, Natalia N; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Spurdle, Amanda B; Wauters, Els; Smeets, Dominiek; Beuselinck, Benoit; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe Grenaker; Zheng, Wei; Hunter, David; Lindstrom, Sara; Hankinson, Susan; Kraft, Phillip; Andrulis, Irene; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Jukkola-Vuorinen, Arja; Grip, Mervi; Kauppila, Saila; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Hollestelle, Antoinette; Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Eccles, Diana M; Rafiq, Sajjad; Tapper, William J; Gerty, Sue M; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Cox, Angela; Reed, Malcolm W R; Luccarini, Craig; Baynes, Caroline; Dunning, Alison M; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rüdiger, Thomas; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Simard, Jacques; Dumont, Martine; Soucy, Penny; Eeles, Rosalind; Muir, Kenneth; Wiklund, Fredrik; Gronberg, Henrik; Schleutker, Johanna; Nordestgaard, Børge G; Weischer, Maren; Travis, Ruth C; Neal, David; Donovan, Jenny L; Hamdy, Freddie C; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Schaid, Daniel J; Kelley, Joseph L; Maier, Christiane; Kibel, Adam; Cybulski, Cezary; Cannon-Albright, Lisa; Butterbach, Katja; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Renner, Stefan P; Hartmann, Arndt; Hein, Alexander; Ruebner, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambretchs, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Nickels, Stefan; Eilber, Ursula; Wang-Gohrke, Shan; Odunsi, Kunle; Sucheston-Campbell, Lara E; Friel, Grace; Lurie, Galina; Killeen, Jeffrey L; Wilkens, Lynne R; Goodman, Marc T; Runnebaum, Ingo; Hillemanns, Peter A; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; Moysich, Kirsten B; du Bois, Andreas; Heitz, Florian; Harter, Philipp; Kommoss, Stefan; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjaer, Susanne Krüger; Høgdall, Estrid; Peissel, Bernard; Bonanni, Bernardo; Bernard, Loris; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Cunningham, Julie M; Larson, Melissa C; Fogarty, Zachary C; Kalli, Kimberly R; Liang, Dong; Lu, Karen H; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Dao, Fanny; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Marks, Jeffrey R; Akushevich, Lucy; Cramer, Daniel; Schildkraut, Joellen; Terry, Kathryn; Poole, Elizabeth M.; Stampfer, Meir; Tworoger, Shelley; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Bjorge, Line; Salvesen, Helga B; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Górski, Bohdan; Gronwald, Jacek; Menkiszak, Janusz; Høgdall, Claus K; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend Aage; Dicks, Ed; Tyrer, Jonathan; Campbell, Ian; McNeish, Iain; Paul, James; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Cai, Hui; Shu, Xiao-Ou; Teten, Rachel T; Sutphen, Rebecca; McLaughlin, John R; Narod, Steven A; Phelan, Catherine M; Monteiro, Alvaro N; Fenstermacher, David; Lin, Hui-Yi; Permuth, Jennifer B; Sellers, Thomas A; Chen, Y Ann; Tsai, Ya-Yu; Chen, Zhihua; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Wu, Anna H; Pearce, Celeste L; Van Den Berg, David; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul DP; Song, Honglin; Winship, Ingrid; Chenevix-Trench, Georgia; Giles, Graham G; Tavtigian, Sean V; Easton, Doug F; Milne, Roger LBackground: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.