The University of Southampton
University of Southampton Institutional Repository

Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.

Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)).

Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers.

Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers.
1055-9965
645-657
Couch, Fergus J.
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Caldes, Trinidad
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de la Hoya, Miguel
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Ding, Yuan Chun
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Chenevix-Trench, Georgia
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Offit, Kenneth
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Simard, Jacques
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Couch, Fergus J., Gaudet, Mia M., Antoniou, Antonis C., Ramus, Susan J., Kuchenbaecker, Karoline B., Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, Wang, Xianshu, Kirchhoff, Tomas, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Sinilnikova, Olga M., Andrulis, Irene L., Ozcelik, Hilmi, Mulligan, Anna Marie, Thomassen, Mads, Gerdes, Anne-Marie, Jensen, Uffe Birk, Skytte, Anne-Bine, Kruse, Torben A., Caligo, Maria A., von Wachenfeldt, Anna, Barbany-Bustinza, Gisela, Loman, Niklas, Soller, Maria, Ehrencrona, Hans, Karlsson, Per, Nathanson, Katherine L., Rebbeck, Timothy R., Domchek, Susan M., Jakubowska, Ania, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Zlowocka, Elżbieta, Huzarski, Tomasz, Byrski, Tomasz, Gronwald, Jacek, Cybulski, Cezary, Gorski, Bohdan, Osorio, Ana, Duran, Mercedes, Tejada, María Isabel, Benitez, Javier, Hamann, Ute, Hogervorst, Frans B.L., van Os, Theo A., van Leeuwen, Flora E., Meijers-Heijboer, Hanne E.J., Wijnen, Juul, Blok, Marinus J., Kets, Marleen, Hooning, Maartje J., Oldenburg, Rogier A., Ausems, Margreet G.E.M., Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth, Jacobs, Chris, Eeles, Rosalind A., Adlard, Julian, Davidson, Rosemarie, Eccles, Diana M., Cole, Trevor, Cook, Jackie, Paterson, Joan, Brewer, Carole, Douglas, Fiona, Hodgson, Shirley V., Morrison, Patrick J., Walker, Lisa, Porteous, Mary E., Kennedy, M. John, Side, Lucy E., Bove, Betsy, Godwin, Andrew K., Stoppa-Lyonnet, Dominique, Fassy-Colcombet, Marion, Castera, Laurent, Cornelis, François, Mazoyer, Sylvie, Leone, Mélanie, Boutry-Kryza, Nadia, Bressac-de Paillerets, Brigitte, Caron, Olivier, Pujol, Pascal, Coupier, Isabelle, Delnatte, Capuchine, Akloul, Linda, Lynch, Henry T., Snyder, Carrie L., Buys, Saundra S., Daly, Mary B., Terry, MaryBeth, Chung, Wendy K., John, Esther M., Miron, Alexander, Southey, Melissa C., Hopper, John L., Goldgar, David E., Singer, Christian F., Rappaport, Christine, Tea, Muy-Kheng M., Fink-Retter, Anneliese, Hansen, Thomas V.O., Nielsen, Finn C., Arason, Aðalgeir, Vijai, Joseph, Shah, Sohela, Sarrel, Kara, Robson, Mark E., Piedmonte, Marion, Phillips, Kelly, Basil, Jack, Rubinstein, Wendy S., Boggess, John, Wakeley, Katie, Ewart-Toland, Amanda, Montagna, Marco, Agata, Simona, Imyanitov, Evgeny N., Isaacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Feliubadalo, Lidia, Brunet, Joan, Gayther, Simon A., Pharoah, Paul P.D., Odunsi, Kunle O., Karlan, Beth Y., Walsh, Christine S., Olah, Edith, Teo, Soo Hwang, Ganz, Patricia A., Beattie, Mary S., van Rensburg, Elizabeth J., Dorfling, Cecelia M., 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, Dorothea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Heinritz, Wolfram, Caldes, Trinidad, de la Hoya, Miguel, Muranen, Tara A., Nevanlinna, Heli, Tischkowitz, Marc D., Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan Chun, Lindor, Noralane M., Fredericksen, Zachary, Pankratz, V. Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Barile, Monica, Bernard, Loris, Viel, Alessandra, Giannini, Giuseppe, Varesco, Liliana, Radice, Paolo, Greene, Mark H., Mai, Phuong L., Easton, Douglas F., Chenevix-Trench, Georgia, Offit, Kenneth and Simard, Jacques (2012) Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiology, Biomarkers & Prevention, 21 (4), 645-657. (doi:10.1158/1055-9965.EPI-11-0888). (PMID:22351618)

Record type: Article

Abstract

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.

Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)).

Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers.

Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers.

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More information

e-pub ahead of print date: 20 February 2012
Published date: April 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352328
URI: http://eprints.soton.ac.uk/id/eprint/352328
ISSN: 1055-9965
PURE UUID: d7b2ebc8-ecbf-455c-8e1d-fb9e6e95c733
ORCID for Diana M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 10 May 2013 08:58
Last modified: 15 Mar 2024 02:40

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Contributors

Author: Fergus J. Couch
Author: Mia M. Gaudet
Author: Antonis C. Antoniou
Author: Susan J. Ramus
Author: Karoline B. Kuchenbaecker
Author: Penny Soucy
Author: Jonathan Beesley
Author: Xiaoqing Chen
Author: Xianshu Wang
Author: Tomas Kirchhoff
Author: Lesley McGuffog
Author: Daniel Barrowdale
Author: Andrew Lee
Author: Sue Healey
Author: Olga M. Sinilnikova
Author: Irene L. Andrulis
Author: Hilmi Ozcelik
Author: Anna Marie Mulligan
Author: Mads Thomassen
Author: Anne-Marie Gerdes
Author: Uffe Birk Jensen
Author: Anne-Bine Skytte
Author: Torben A. Kruse
Author: Maria A. Caligo
Author: Anna von Wachenfeldt
Author: Gisela Barbany-Bustinza
Author: Niklas Loman
Author: Maria Soller
Author: Hans Ehrencrona
Author: Per Karlsson
Author: Katherine L. Nathanson
Author: Timothy R. Rebbeck
Author: Susan M. Domchek
Author: Ania Jakubowska
Author: Jan Lubinski
Author: Katarzyna Jaworska
Author: Katarzyna Durda
Author: Elżbieta Zlowocka
Author: Tomasz Huzarski
Author: Tomasz Byrski
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