Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

Abstract:

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 \times 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 \times 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 \times 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

DOI: 10.1002/humu.22025

Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Publication type: Journal article

Journal: Human mutation

Human Diseases: Hereditary breast ovarian cancer syndrome

Citation: Hum. Mutat. 33(4):690-702

Date Published: 1st Apr 2012

Registered Mode: imported from a bibtex file

Authors: Susan J. Ramus, Antonis C. Antoniou, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Daniel Barrowdale, Andrew Lee, Mads Thomassen, Anne-Marie Gerdes, Torben A. Kruse, Uffe Birk Jensen, Anne-Bine Skytte, Maria A. Caligo, Annelie Liljegren, Annika Lindblom, Håkan Olsson, Ulf Kristoffersson, Marie Stenmark-Askmalm, Beatrice Melin, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Cezary Cybulski, Aleksandra Toloczko-Grabarek, Ana Osorio, Javier Benitez, Mercedes Duran, Maria-Isabel Tejada, Ute Hamann, Matti Rookus, Flora E. van Leeuwen, Cora M. Aalfs, Hanne E. J. Meijers-Heijboer, Christi J. van Asperen, K. E. P. van Roozendaal, Nicoline Hoogerbrugge, J. Margriet Collée, Mieke Kriege, Rob B. van der Luijt, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Fiona Lalloo, Chris Jacobs, Ros Eeles, Julian Adlard, Rosemarie Davidson, Diana Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Fiona Douglas, Carole Brewer, Shirley Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Harsh Pathak, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Virginie Caux-Moncoutier, Antoine de Pauw, Marion Gauthier-Villars, Sylvie Mazoyer, Mélanie Léoné, Alain Calender, Christine Lasset, Valérie Bonadona, Agnès Hardouin, Pascaline Berthet, Yves-Jean Bignon, Nancy Uhrhammer, Laurence Faivre, Catherine Loustalot, Saundra Buys, Mary Daly, Alex Miron, Mary Beth Terry, Wendy K. Chung, Esther M. John, Melissa Southey, David Goldgar, Christian F. Singer, Muy-Kheng Tea, Georg Pfeiler, Anneliese Fink-Retter, Thomas v. O. Hansen, Bent Ejlertsen, Oskar Th Johannsson, Kenneth Offit, Tomas Kirchhoff, Mia M. Gaudet, Joseph Vijai, Mark Robson, Marion Piedmonte, Kelly-Anne Phillips, Linda van Le, James S. Hoffman, Amanda Ewart Toland, Marco Montagna, Silvia Tognazzo, Evgeny Imyanitov, Claudine Issacs, Ramunas Janavicius, Conxi Lazaro, Iganacio Blanco, Eva Tornero, Matilde Navarro, Kirsten B. Moysich, Beth Y. Karlan, Jenny Gross, Edith Olah, Tibor Vaszko, Soo-Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorotehea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Dieter Schäfer, Trinidad Caldes, Miguel de La Hoya, Heli Nevanlinna, Kristiina Aittomäki, Marie Plante, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Xianshu Wang, Noralane Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Bernardo Bonanni, Loris Bernard, Riccardo Dolcetti, Laura Papi, Laura Ottini, Paolo Radice, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Paul D. P. Pharoah, Simon A. Gayther, Jacques Simard, Douglas F. Easton, Fergus J. Couch, Georgia Chenevix-Trench

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René Hänsel

Citation

Ramus, S. J., Antoniou, A. C., Kuchenbaecker, K. B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Sinilnikova, O. M., Healey, S., Barrowdale, D., Lee, A., Thomassen, M., Gerdes, A.-M., Kruse, T. A., Jensen, U. B., Skytte, A.-B., Caligo, M. A., Liljegren, A., Lindblom, A., … . (2012). Ovarian cancer susceptibility alleles and risk of ovarian cancer inBRCA1andBRCA2mutation carriers. In Human Mutation (Vol. 33, Issue 4, pp. 690–702). Wiley. https://doi.org/10.1002/humu.22025

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Created: 15th Jul 2020 at 13:30

Last updated: 7th Dec 2021 at 17:58

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

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