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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.

Couch, Fergus J; Gaudet, Mia M; Antoniou, Antonis C; Ramus, Susan J; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; Wang, Xianshu and Kirchhoff, Tomas, et al. (2012) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 21(4). p.645-657
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... (More)
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. Cancer Epidemiol Biomarkers Prev; ©2012 AACR. (Less)
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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
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21
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4
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645 - 657
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American Association for Cancer Research
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  • wos:000302220600010
  • pmid:22351618
  • scopus:84859377440
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-11-0888
language
English
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yes
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http://www.ncbi.nlm.nih.gov/pubmed/22351618?dopt=Abstract
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2012-03-02 13:16:21
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@article{5d22b7f0-abb7-4d46-b643-40260854db30,
  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).<br/><br>
<br/><br>
METHODS: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.<br/><br>
<br/><br>
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)).<br/><br>
<br/><br>
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. Cancer Epidemiol Biomarkers Prev; ©2012 AACR.},
  author       = {Couch, Fergus J and Gaudet, Mia M and Antoniou, Antonis C and Ramus, Susan J and Kuchenbaecker, Karoline B and Soucy, Penny and Beesley, Jonathan and Chen, Xiaoqing and Wang, Xianshu and Kirchhoff, Tomas and McGuffog, Lesley and Barrowdale, Daniel and Lee, Andrew and Healey, Sue and Sinilnikova, Olga M and Andrulis, Irene L and Ozcelik, Hilmi and Mulligan, Anna Marie and Thomassen, Mads and Gerdes, Anne-Marie and Jensen, Uffe Birk and Skytte, Anne-Bine and Kruse, Torben A and Caligo, Maria A and von Wachenfeldt, Anna and Barbany-Bustinza, Gisela and Loman, Niklas and Soller, Maria and Ehrencrona, Hans and Karlsson, Per and Nathanson, Katherine L and Rebbeck, Timothy R and Domchek, Susan M and Jakubowska, Ania and Lubinski, Jan and Jaworska, Katarzyna and Durda, Katarzyna and Zlowocka, Elzbieta and Huzarski, Tomasz and Byrski, Tomasz and Gronwald, Jacek and Cybulski, Cezary and Górski, Bohdan and Osorio, Ana and Durán, Mercedes and Tejada, María Isabel and Benitez, Javier and Hamann, Ute and Hogervorst, Frans B L and van Os, Theo A and van Leeuwen, Flora E and Meijers-Heijboer, Hanne E J and Wijnen, Juul and Blok, Marinus J and Kets, Marleen and Hooning, Maartje J and Oldenburg, Rogier A and Ausems, Margreet G E M and Peock, Susan and Frost, Debra and Ellis, Steve D and Platte, Radka and Fineberg, Elena and Evans, D Gareth and Jacobs, Chris and Eeles, Rosalind A and Adlard, Julian and Davidson, Rosemarie and Eccles, Diana M and Cole, Trevor and Cook, Jackie and Paterson, Joan and Brewer, Carole and Douglas, Fiona and Hodgson, Shirley V and Morrison, Patrick J and Walker, Lisa and Porteous, Mary E and Kennedy, M John and Side, Lucy E and Bove, Betsy and Godwin, Andrew K and Stoppa-Lyonnet, Dominique and Fassy-Colcombet, Marion and Castera, Laurent and Cornelis, François and Mazoyer, Sylvie and Léoné, Mélanie and Boutry-Kryza, Nadia and Bressac-de Paillerets, Brigitte and Caron, Olivier and Pujol, Pascal and Coupier, Isabelle and Delnatte, Capucine and Akloul, Linda and Lynch, Henry T and Snyder, Carrie L and Buys, Saundra S and Daly, Mary B and Terry, Marybeth and Chung, Wendy K and John, Esther M and Miron, Alexander and Southey, Melissa C and Hopper, John L and Goldgar, David E and Singer, Christian F and Rappaport, Christine and Tea, Muy-Kheng M and Fink-Retter, Anneliese and Hansen, Thomas V O and Nielsen, Finn C and Arason, Aðalgeir and Vijai, Joseph and Shah, Sohela and Sarrel, Kara and Robson, Mark E and Piedmonte, Marion and Phillips, Kelly and Basil, Jack and Rubinstein, Wendy S and Boggess, John and Wakeley, Katie and Ewart-Toland, Amanda and Montagna, Marco and Agata, Simona and Imyanitov, Evgeny N and Isaacs, Claudine and Janavicius, Ramunas and Lazaro, Conxi and Blanco, Ignacio and Feliubadalo, Lidia and Brunet, Joan and Gayther, Simon A and Pharoah, Paul P D and Odunsi, Kunle O and Karlan, Beth Y and Walsh, Christine S and Olah, Edith and Teo, Soo Hwang and Ganz, Patricia A and Beattie, Mary S and van Rensburg, Elizabeth J and Dorfling, Cecelia M and Diez, Orland and Kwong, Ava and Schmutzler, Rita K and Wappenschmidt, Barbara and Engel, Christoph and Meindl, Alfons and Ditsch, Nina and Arnold, Norbert and Heidemann, Simone and Niederacher, Dieter and Preisler-Adams, Sabine and Gadzicki, Dorothea and Varon-Mateeva, Raymonda and Deissler, Helmut and Gehrig, Andrea and Sutter, Christian and Kast, Karin and Fiebig, Britta and Heinritz, Wolfram and Caldes, Trinidad and de la Hoya, Miguel and Muranen, Taru A and Nevanlinna, Heli and Tischkowitz, Marc D and Spurdle, Amanda B and Neuhausen, Susan L and Ding, Yuan Chun and Lindor, Noralane M and Fredericksen, Zachary and Pankratz, V Shane and Peterlongo, Paolo and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Barile, Monica and Bernard, Loris and Viel, Alessandra and Giannini, Giuseppe and Varesco, Liliana and Radice, Paolo and Greene, Mark H and Mai, Phuong L and Easton, Douglas F and Chenevix-Trench, Georgia and Offit, Kenneth and Simard, Jacques},
  issn         = {1538-7755},
  language     = {eng},
  number       = {4},
  pages        = {645--657},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
  title        = {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.},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-11-0888},
  volume       = {21},
  year         = {2012},
}