The University of Southampton
University of Southampton Institutional Repository

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

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
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.
ovarian cancer, BRCA1, BRCA2, association, SNP
1059-7794
690-702
Ramus, Susan J.
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Antoniou, Antonis C.
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Kuchenbaecker, Karoline B.
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Soucy, Penny
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Beesley, Jonathan
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Chen, Xiaoqing
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McGuffog, Lesley
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Sinilnikova, Olga M.
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Healey, Sue
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Barrowdale, Daniel
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Lee, Andrew
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Thomassen, Mads
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Olsson, Håkan
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Domchek, Susan M.
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Nathanson, Katherine L.
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de Pauw, Antoine
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Byrski, Tomasz
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Hamann, Ute
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Aalfs, Cora M.
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Meijers-Heijboer, Hanne E.J.
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van Asperen, Christi J.
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Ellis, Steve D.
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Platte, Radka
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Fineberg, Elena
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Evans, D. Gareth
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Lalloo, Fiona
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Jacobs, Chris
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Eeles, Ros
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Adlard, Julian
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Pfeiler, Georg
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Ejlertsen, Bent
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Johannsson, Oskar Th.
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Offit, Kenneth
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Kirchhoff, Tomas
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Phillips, Kelly-Anne
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Van Le, Linda
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Hoffman, James S
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Toland, Amanda Ewart
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Montagna, Marco
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Tognazzo, Silvia
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Imyanitov, Evgeny
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Isaacs, Claudine
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Janavicius, Ramunas
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Lazaro, Conxi
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Tornero, Eva
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Moysich, Kirsten B.
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Wappenschmidt, Barbara
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Engel, Christoph
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Caldes, Trinidad
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de la Hoya, Miguel
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Nevanlinna, Heli
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Aittomäki, Kristiina
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Spurdle, Amanda B.
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Neuhausen, Susan L.
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Ding, Yuan Chun
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Bernard, Loris
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Dolcetti, Riccardo
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Mai, Phuong L.
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Andrulis, Irene L.
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Ozcelik, Hilmi
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Pharoah, Paul D.P.
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Gayther, Simon A.
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Simard, Jacques
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Easton, Douglas F.
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Couch, Fergus J.
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Chenevix-Trench, Georgia
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Ramus, Susan J., Antoniou, Antonis C., Kuchenbaecker, Karoline B., Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Sinilnikova, Olga M., Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A., Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A., Liljegren, Annelie, Lindblom, Annika, Olsson, Håkan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M., Nathanson, Katherine L., Rebbeck, Timothy R., Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Tejada, Maria-Isabel, Hamann, Ute, Rookus, Matti, van Leeuwen, Flora E., Aalfs, Cora M., Meijers-Heijboer, Hanne E.J., van Asperen, Christi J., van Roozendaal, K.E.P., Hoogerbrugge, Nicoline, Collée, J. Margriet, Kriege, Mieke, van der Luijt, Rob B., Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth, Lalloo, Fiona, Jacobs, Chris, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Paterson, Joan, Douglas, Fiona, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J., Walker, Lisa, Porteous, Mary E., Kennedy, M. John, Pathak, Harsh, Godwin, Andrew K., Stoppa-Lyonnet, Dominique, Caux-Moncoutier, Virginie, de Pauw, Antoine, Gauthier-Villars, Marion, Mazoyer, Sylvie, Léoné, Mélanie, Calender, Alain, Lasset, Christine, Bonadona, Valérie, Hardouin, Agnès, Berthet, Pascaline, Bignon, Yves-Jean, Uhrhammer, Nancy, Faivre, Laurence, Loustalot, Catherine, Buys, Saundra, Daly, Mary, Miron, Alex, Beth Terry, Mary, Chung, Wendy K., John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F., Tea, Muy-Kheng, Pfeiler, Georg, Fink-Retter, Anneliese, Hansen, Thomas v. O., Ejlertsen, Bent, Johannsson, Oskar Th., Offit, Kenneth, Kirchhoff, Tomas, Gaudet, Mia M., Vijai, Joseph, Robson, Mark, Piedmonte, Marion, Phillips, Kelly-Anne, Van Le, Linda, Hoffman, James S, Toland, Amanda Ewart, Montagna, Marco, Tognazzo, Silvia, Imyanitov, Evgeny, Isaacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Tornero, Eva, Navarro, Matilde, Moysich, Kirsten B., Karlan, Beth Y., Gross, Jenny, Olah, Edith, Vaszko, Tibor, Teo, Soo-Hwang, Ganz, Patricia A., Beattie, Mary S., Dorfling, Cecelia M, van Rensburg, Elizabeth J., Diez, Orland, Kwong, Ava, Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Heidemann, Simone, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Schäfer, Dieter, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Plante, Marie, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan Chun, Wang, Xianshu, Lindor, Noralane, Fredericksen, Zachary, Pankratz, V. Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Bonanni, Bernardo, Bernard, Loris, Dolcetti, Riccardo, Papi, Laura, Ottini, Laura, Radice, Paolo, Greene, Mark H., Mai, Phuong L., Andrulis, Irene L., Glendon, Gord, Ozcelik, Hilmi, Pharoah, Paul D.P., Gayther, Simon A., Simard, Jacques, Easton, Douglas F., Couch, Fergus J. and Chenevix-Trench, Georgia (2012) Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Human Mutation, 33 (4), 690-702. (doi:10.1002/humu.22025). (PMID:22253144)

Record type: Article

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.

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More information

e-pub ahead of print date: 14 February 2012
Published date: April 2012
Keywords: ovarian cancer, BRCA1, BRCA2, association, SNP
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352337
URI: https://eprints.soton.ac.uk/id/eprint/352337
ISSN: 1059-7794
PURE UUID: e08b947e-1e5a-4979-b623-a3e187779929

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Date deposited: 10 May 2013 15:13
Last modified: 16 Jul 2019 21:34

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Contributors

Author: Susan J. Ramus
Author: Antonis C. Antoniou
Author: Karoline B. Kuchenbaecker
Author: Penny Soucy
Author: Jonathan Beesley
Author: Xiaoqing Chen
Author: Lesley McGuffog
Author: Olga M. Sinilnikova
Author: Sue Healey
Author: Daniel Barrowdale
Author: Andrew Lee
Author: Mads Thomassen
Author: Anne-Marie Gerdes
Author: Torben A. Kruse
Author: Uffe Birk Jensen
Author: Anne-Bine Skytte
Author: Maria A. Caligo
Author: Annelie Liljegren
Author: Annika Lindblom
Author: Håkan Olsson
Author: Ulf Kristoffersson
Author: Marie Stenmark-Askmalm
Author: Beatrice Melin
Author: Susan M. Domchek
Author: Katherine L. Nathanson
Author: Timothy R. Rebbeck
Author: Anna Jakubowska
Author: Jan Lubinski
Author: Katarzyna Jaworska
Author: Katarzyna Durda
Author: Elżbieta Złowocka
Author: Jacek Gronwald
Author: Tomasz Huzarski
Author: Tomasz Byrski
Author: Cezary Cybulski
Author: Aleksandra Toloczko-Grabarek
Author: Ana Osorio
Author: Javier Benitez
Author: Mercedes Duran
Author: Maria-Isabel Tejada
Author: Ute Hamann
Author: Matti Rookus
Author: Flora E. van Leeuwen
Author: Cora M. Aalfs
Author: Hanne E.J. Meijers-Heijboer
Author: Christi J. van Asperen
Author: K.E.P. van Roozendaal
Author: Nicoline Hoogerbrugge
Author: J. Margriet Collée
Author: Mieke Kriege
Author: Rob B. van der Luijt
Author: Susan Peock
Author: Debra Frost
Author: Steve D. Ellis
Author: Radka Platte
Author: Elena Fineberg
Author: D. Gareth Evans
Author: Fiona Lalloo
Author: Chris Jacobs
Author: Ros Eeles
Author: Julian Adlard
Author: Rosemarie Davidson
Author: Diana Eccles
Author: Trevor Cole
Author: Jackie Cook
Author: Joan Paterson
Author: Fiona Douglas
Author: Carole Brewer
Author: Shirley Hodgson
Author: Patrick J. Morrison
Author: Lisa Walker
Author: Mary E. Porteous
Author: M. John Kennedy
Author: Harsh Pathak
Author: Andrew K. Godwin
Author: Dominique Stoppa-Lyonnet
Author: Virginie Caux-Moncoutier
Author: Antoine de Pauw
Author: Marion Gauthier-Villars
Author: Sylvie Mazoyer
Author: Mélanie Léoné
Author: Alain Calender
Author: Christine Lasset
Author: Valérie Bonadona
Author: Agnès Hardouin
Author: Pascaline Berthet
Author: Yves-Jean Bignon
Author: Nancy Uhrhammer
Author: Laurence Faivre
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