Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2012 Apr;33(4):690-702.
doi: 10.1002/humu.22025. Epub 2012 Feb 14.

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

Susan J Ramus  1 , 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; SWE-BRCA; 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; HEBON; EMBRACE; 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; GEMO; 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; kConFab; 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; OCGN; Paul D P Pharoah, Simon A Gayther, Jacques Simard, Douglas F Easton, Fergus J Couch, Georgia Chenevix-Trench; Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
Collaborators, Affiliations
Multicenter Study

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

Susan J Ramus et al. Hum Mutat. 2012 Apr.

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 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 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 × 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Forest plots of study-specific HRs for ovarian cancer risk in (a) BRCA1 mutation carriers, (b) BRCA2 mutation carriers. Country-specific per-allele HR estimates for the SNPs rs10088218 (8q24), rs2665390 (3q25), rs717852 (2q31), and rs9303542 (17q21) in BRCA1 and BRCA2 mutation carriers. The area of the square is proportional to the inverse of the variance of the estimate. Horizontal lines indicate 95% confidence intervals. Diamonds indicate the summary HR estimates for all of the CIMBA. For BRCA2, some of the smaller studies have been combined with others from the same country. GE/AT/HU denotes the stratum for Germany, Austria, and Hungary. NL/SA denotes the stratum for the Netherlands and South Africa.
See this image and copyright information in PMC

References

    1. Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, et al. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet. 2009;41:585–590. - PMC - PubMed
    1. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117–1130. - PMC - PubMed
    1. Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL, Ding YC, Rebbeck TR, Weitzel JN, Lynch HT, Isaacs C, Ganz PA, et al. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction. Cancer Res. 2010b;70:9742–9754. - PMC - PubMed
    1. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Brit J Cancer. 2008b;98:1457–1466. - PMC - PubMed
    1. Antoniou AC, Kartsonaki C, Sinilnikova OM, Soucy P, McGuffog L, Healey S, Lee A, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Cattaneo E, et al. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet. 2011;20:3304–3321. Advanced access published on 18 May 2011. - PMC - PubMed

Publication types

Grants and funding