Identification of six new susceptibility loci for invasive epithelial ovarian cancer Journal Article


Authors: Kuchenbaecker, K. B.; Ramus, S. J.; Tyrer, J.; Lee, A.; Shen, H. C.; Beesley, J.; Lawrenson, K.; McGuffog, L.; Healey, S.; Lee, J. M.; Spindler, T. J.; Lin, Y. G.; Pejovic, T.; Bean, Y.; Li, Q.; Coetzee, S.; Hazelett, D.; Miron, A.; Southey, M.; Terry, M. B.; Goldgar, D. E.; Buys, S. S.; Janavicius, R.; Dorfling, C. M.; van Rensburg, E. J.; Neuhausen, S. L.; Ding, Y. C.; Hansen, T. V. O.; Jonson, L.; Gerdes, A. M.; Ejlertsen, B.; Barrowdale, D.; Dennis, J.; Benitez, J.; Osorio, A.; Jose Garcia, M.; Komenaka, I.; Weitzel, J. N.; Ganschow, P.; Peterlongo, P.; Bernard, L.; Viel, A.; Bonanni, B.; Peissel, B.; Manoukian, S.; Radice, P.; Papi, L.; Pttini, L.; Fostira, F.; Konstantopoulou, I.; Garber, J.; Frost, D.; Perkins, J.; Platte, R.; Ellis, S.; EMBRACE; Godwin, A. K.; Schmutzler, R. K.; Meindl, A.; Engel, C.; Sutter, C.; Sinilnikova, O. M.; GEMO Study Collaborators; Damiola, F.; Mazoyer, S.; Stoppa-Lyonnet, D.; Claes, K.; De Leeneer, K.; Kirk, J.; Rodriguez, G. C.; Piedmonte, M.; O'Malley, D. M.; de la Hoya, M.; Caldes, T.; Aittomaki, K.; Nevanlinna, H.; Collee, J. M.; Rookus, M. A.; Oosterwijk, J. C.; Breast Cancer Family Registry; Tihomirova, L.; Tung, N.; Hamann, U.; Isacca, C.; Tischkowitz, M.; Imyanitov, E. N.; Caligo, M. A.; Campbell, I G.; Hogervorst, F. B. L.; HEBON; Olah, E.; Diez, O.; Blanco, I.; Brunet, J.; Lazaro, C.; Pujana, M. A.; Jakubowska, A.; Gronwald, J.; Lubinski, J.; Sukiennicki, G.; Barkardottir, R. B.; Plante, M.; Simard, J.; Soucy, P.; Monyahna, M.; Tognazzo, S.; Teixeira, M. R.; KConFab Investigators; Pankratz, V. S.; Wang, X.; Lindor, N.; Szabo, C. I.; Kauff, N.; Vijai, J.; Aghajanian, C. A.; Pfeiler, G.; Berger, A.; Singer, C. F.; Tea, M. K.; Phelan, C. M.; Greene, M. H.; Mai, P. L.; Rennert, G.; Mulligan, A. M.; Tchatchou, S.; Andrulis, I. L.; Glendon, G.; Toland, A. E.; Jensen, U. B.; Kruse, T. A.; Thomassen, M.; Bojesen, A.; Zidan, J.; Friedman, E.; Laitman, Y.; Soller, M.; Liljegren, A.; Arver, B.; Einbeigi, Z.; Stenmark-Askmalm, M.; Olopade, O. I.; Nussbaum, R. L.; Rebbeck, T. R.; Nathanson, K. L.; Domchek, S. M.; Lu, K. H.; Karlan, B. Y.; Walsh, C.; Lester, J.; Australian Cancer Study (Ovarian Cancer Investigators); Australian Ovarian Cancer Study Group; Hein, A.; Ekici, A. B.; Beckmann, M. W.; Fasching, P. A.; Lambrechts, D.; Van Nieuwenhuysen, E.; Vergote, I.; Lambrechts, S.; Dicks, E.; Doherty, J. A.; Wicklund, K. G.; Rossing, M. A.; Rudolph, A.; Chang-Claude, J.; Wang-Gohrke, S.; Eilber, U.; Moysich, K. B.; Odunsi, K.; Sucheston, L.; Lele, S.; Wilkens, L. R.; Goodman, M. T.; Thompson, P. J.; Shvetsov, Y. B.; Runnebaum, I. B.; Durst, M.; Hillemanns, P.; Dork, T.; Antonenkova, N.; Bogdanova, N.; Leminen, A.; Pelttari, L. M.; Butzow, R.; Modugno, F.; Kelley, J. L.; Edwards, R. P.; Ness, R. B.; du Bois, A.; Heitz, F.; Schwaab, I.; Harter, P.; Matsuo, K.; Hosono, S.; Orsulic, S.; Jensen, A.; Kruger Kjaer, S.; Hogdall, E.; Hasmad, H. N.; Azmi, M. A. N.; Teo, S. H.; Woo, Y. L.; Fridley, B. L.; Goode, E. L.; Cunningham, J. M.; Vierkant, R. A.; Bruinsma, F.; Giles, G. G.; Liang, D.; Hildebrandt, M. A. T.; Wu, X.; Levine, D. A.; Bisogna, M.; Berchuck, A.; Iversen, E. S.; Schildkraut, J. M.; Concannon, P.; Palmieri Weber, R.; Cramer, D. W.; Terry, K. L.; Poole, E. M.; Tworoger, S. S.; Bandera, E. V.; Orlow, I.; Olson, S. H.; Krakstad, C.; Salvesen, H. B.; Tangen, I. L.; Bjorge, L.; van Altena, A. M.; Aben, K. K. H.; Kiemeney, L. A.; Massuger, L. F. A. G.; Kellar, M.; Brooks-Wilson, A.; Kelemen, L. E.; Cook, L. S.; Le, N. D.; Cybulski, C.; Yang, H.; Lissowska, J.; Brinton, L. A.; Wentzensen, N.; Wentzensen, N.; Lundvall, L.; Nedergaard, L.; Baker, H.; Song, H.; Eccles, D.; McNeish, I.; Paul, J.; Carty, K.; Siddiqui, N.; Glasspool, R.; Whittemore, A. S.; Rothstein, J. H.; McGuire, V.; Sieh, W.; Ji, B. T.; Zheng, W.; Shu, X. O.; Gao, Y. T.; Rosen, B.; Risch, H. A.; McLaughlin, J. R.; Narod, S. A.; Monteiro, A. N.; Chen, A.; Lin, H. Y.; Permuth-Wey, J.; Sellers, T. A.; Tsai, Y. Y.; Chen, Z.; Ziogas, A.; Anton-Culver, H.; Gentry-Maharaj, A.; Menon, U.; Harrington, P.; Lee, A. W.; Wu, A. H.; Pearce, C. L.; Coetzee, G.; Pike, M. C.; Dansonka-Mieszkowska, A.; Timorek, A.; Rzepecka, I. K.; Kupryjanczyk, J.; Freedman, M.; Noushmehr, H.; Easton, D. F.; Offit, K.; Couch, F. J.; Gayther, S.; Pharoah, P. P.; Antoniou, A. C.; Chenevix-Trench, G.; for the Consortium of Investigators of Modifiers of BRCA1 and BRCA2
Article Title: Identification of six new susceptibility loci for invasive epithelial ovarian cancer
Abstract: Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
Keywords: risk; breast-cancer; genome-wide association; metaanalysis; myopodin; brca2 mutation carriers; common variants; genetic-variation; abo blood-group; human elg1
Journal Title: Nature Genetics
Volume: 47
Issue: 2
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2015-02-01
Start Page: 164
End Page: 171
Language: English
ACCESSION: WOS:000348694700012
DOI: 10.1038/ng.3185
PROVIDER: wos
PUBMED: 25581431
PMCID: PMC4445140
Notes: Article -- Source: Wos
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  1. Malcolm Pike
    133 Pike
  2. Kenneth Offit
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  3. Sara H Olson
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  4. Noah Kauff
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  5. Douglas A Levine
    356 Levine
  6. Irene Orlow
    192 Orlow
  7. Vijai Joseph
    120 Joseph