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

Fergus J. Couch, Mia M. Gaudet, Antonis C. Antoniou, Susan J. Ramus, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Xianshu Wang, Tomas Kirchhoff, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Sue Healey, Olga M. Sinilnikova, Irene L. Andrulis, Hilmi Ozcelik, Anna Marie Mulligan, Mads Thomassen, Anne Marie GerdesUffe Birk Jensen, Anne Bine Skytte, Torben A. Kruse, Maria A. Caligo, Anna Von Wachenfeldt, Gisela Barbany-Bustinza, Niklas Loman, Maria Soller, Hans Ehrencrona, Per Karlsson, Katherine Nathanson, Timothy R. Rebbeck, Susan M. Domchek, Ania Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elzbieta Zołwocka, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Cezary Cybulski, Bohdan Goŕski, Ana Osorio, Mercedes Durań, María Isabel Tejada, Javier Benitez, Ute Hamann, Frans B L Hogervorst, Theo A. Van Os, Flora E. Van Leeuwen, Hanne E J Meijers-Heijboer, Juul Wijnen, Marinus J. Blok, Marleen Kets, Maartje J. Hooning, Rogier A. Oldenburg, Margreet G E M Ausems, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Chris Jacobs, Rosalind A. Eeles, Julian Adlard, Rosemarie Davidson, Diana M. Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Carole Brewer, Fiona Douglas, Shirley V. Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Lucy E. Side, Betsy Bove, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Marion Fassy-Colcombet, Laurent Castera, Franco̧is Cornelis, Sylvie Mazoyer, Meĺanie Leóne, Nadia Boutry-Kryza, Brigitte Bressac-de Paillerets, Olivier Caron, Pascal Pujol, Isabelle Coupier, Capucine Delnatte, Linda Akloul, Henry T. Lynch, Carrie L. Snyder, Saundra S. Buys, Mary B. Daly, Mary Beth Terry, Wendy K. Chung, Esther M. John, Alexander Miron, Melissa C. Southey, John L. Hopper, David E. Goldgar, Christian F. Singer, Christine Rappaport, Muy Kheng M Tea, Anneliese Fink-Retter, Thomas V O Hansen, Finn C. Nielsen, Aoalgeir Arason, Joseph Vijai, Sohela Shah, Kara Sarrel, Mark E. Robson, Marion Piedmonte, Kelly Phillips, Jack Basil, Wendy S. Rubinstein, John Boggess, Katie Wakeley, Amanda Ewart-Toland, Marco Montagna, Simona Agata, Evgeny N. Imyanitov, Claudine Isaacs, Ramunas Janavicius, Conxi Lazaro, Ignacio Blanco, Lidia Feliubadalo, Joan Brunet, Simon A. Gayther, Paul P D Pharoah, Kunle O. Odunsi, Beth Y. Karlan, Christine S. Walsh, Edith Olah, Soo Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Elizabeth J. Van Rensburg, Cecelia M. Dorfling, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorothea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Wolfram Heinritz, Trinidad Caldes, Miguel De La Hoya, Taru A. Muranen, Heli Nevanlinna, Marc D. Tischkowitz, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Noralane M. Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Monica Barile, Loris Bernard, Alessandra Viel, Giuseppe Giannini, Liliana Varesco, Paolo Radice, Mark H. Greene, Phuong L. Mai, Douglas F. Easton, Georgia Chenevix-Trench, Kenneth Offit, Jacques Simard

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.Wealso 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.

Original languageEnglish
Pages (from-to)645-657
Number of pages13
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number4
DOIs
StatePublished - Apr 2012

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Estrogen Receptors
Ovarian Neoplasms
Breast Neoplasms
Mutation
Confidence Intervals
Genome-Wide Association Study
Neoplasms
Research Personnel

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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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; 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; Rebbeck, Timothy R.; Domchek, Susan M.; Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zołwocka, Elzbieta; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Cybulski, Cezary; Goŕski, Bohdan; Osorio, Ana; Durań, 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, Franco̧is; Mazoyer, Sylvie; Leóne, Meĺanie; Boutry-Kryza, Nadia; Bressac-de Paillerets, Brigitte; Caron, Olivier; Pujol, Pascal; Coupier, Isabelle; Delnatte, Capucine; Akloul, Linda; Lynch, Henry T.; Snyder, Carrie L.; Buys, Saundra S.; Daly, Mary B.; Terry, Mary Beth; 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, Aoalgeir; 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, Taru 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; Simard, Jacques.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 4, 04.2012, p. 645-657.

Research output: Contribution to journalArticle

Couch, FJ, Gaudet, MM, Antoniou, AC, Ramus, SJ, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, X, Wang, X, Kirchhoff, T, McGuffog, L, Barrowdale, D, Lee, A, Healey, S, Sinilnikova, OM, Andrulis, IL, Ozcelik, H, Mulligan, AM, Thomassen, M, Gerdes, AM, Jensen, UB, Skytte, AB, Kruse, TA, Caligo, MA, Von Wachenfeldt, A, Barbany-Bustinza, G, Loman, N, Soller, M, Ehrencrona, H, Karlsson, P, Nathanson, K, Rebbeck, TR, Domchek, SM, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zołwocka, E, Huzarski, T, Byrski, T, Gronwald, J, Cybulski, C, Goŕski, B, Osorio, A, Durań, M, Tejada, MI, Benitez, J, Hamann, U, Hogervorst, FBL, Van Os, TA, Van Leeuwen, FE, Meijers-Heijboer, HEJ, Wijnen, J, Blok, MJ, Kets, M, Hooning, MJ, Oldenburg, RA, Ausems, MGEM, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Jacobs, C, Eeles, RA, Adlard, J, Davidson, R, Eccles, DM, Cole, T, Cook, J, Paterson, J, Brewer, C, Douglas, F, Hodgson, SV, Morrison, PJ, Walker, L, Porteous, ME, Kennedy, MJ, Side, LE, Bove, B, Godwin, AK, Stoppa-Lyonnet, D, Fassy-Colcombet, M, Castera, L, Cornelis, F, Mazoyer, S, Leóne, M, Boutry-Kryza, N, Bressac-de Paillerets, B, Caron, O, Pujol, P, Coupier, I, Delnatte, C, Akloul, L, Lynch, HT, Snyder, CL, Buys, SS, Daly, MB, Terry, MB, Chung, WK, John, EM, Miron, A, Southey, MC, Hopper, JL, Goldgar, DE, Singer, CF, Rappaport, C, Tea, MKM, Fink-Retter, A, Hansen, TVO, Nielsen, FC, Arason, A, Vijai, J, Shah, S, Sarrel, K, Robson, ME, Piedmonte, M, Phillips, K, Basil, J, Rubinstein, WS, Boggess, J, Wakeley, K, Ewart-Toland, A, Montagna, M, Agata, S, Imyanitov, EN, Isaacs, C, Janavicius, R, Lazaro, C, Blanco, I, Feliubadalo, L, Brunet, J, Gayther, SA, Pharoah, PPD, Odunsi, KO, Karlan, BY, Walsh, CS, Olah, E, Teo, SH, Ganz, PA, Beattie, MS, Van Rensburg, EJ, Dorfling, CM, Diez, O, Kwong, A, Schmutzler, RK, Wappenschmidt, B, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Heidemann, S, Niederacher, D, Preisler-Adams, S, Gadzicki, D, Varon-Mateeva, R, Deissler, H, Gehrig, A, Sutter, C, Kast, K, Fiebig, B, Heinritz, W, Caldes, T, De La Hoya, M, Muranen, TA, Nevanlinna, H, Tischkowitz, MD, Spurdle, AB, Neuhausen, SL, Ding, YC, Lindor, NM, Fredericksen, Z, Pankratz, VS, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Barile, M, Bernard, L, Viel, A, Giannini, G, Varesco, L, Radice, P, Greene, MH, Mai, PL, Easton, DF, Chenevix-Trench, G, Offit, K & Simard, J 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 and Prevention, vol. 21, no. 4, pp. 645-657. https://doi.org/10.1158/1055-9965.EPI-11-0888
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 ; Rebbeck, Timothy R. ; Domchek, Susan M. ; Jakubowska, Ania ; Lubinski, Jan ; Jaworska, Katarzyna ; Durda, Katarzyna ; Zołwocka, Elzbieta ; Huzarski, Tomasz ; Byrski, Tomasz ; Gronwald, Jacek ; Cybulski, Cezary ; Goŕski, Bohdan ; Osorio, Ana ; Durań, 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, Franco̧is ; Mazoyer, Sylvie ; Leóne, Meĺanie ; Boutry-Kryza, Nadia ; Bressac-de Paillerets, Brigitte ; Caron, Olivier ; Pujol, Pascal ; Coupier, Isabelle ; Delnatte, Capucine ; Akloul, Linda ; Lynch, Henry T. ; Snyder, Carrie L. ; Buys, Saundra S. ; Daly, Mary B. ; Terry, Mary Beth ; 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, Aoalgeir ; 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, Taru 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 ; Simard, Jacques. / 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. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 4. pp. 645-657.
@article{d7a6ee2b34fd4781a548997dcada5511,
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",
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.Wealso 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.",
author = "Couch, {Fergus J.} and Gaudet, {Mia M.} and Antoniou, {Antonis C.} and Ramus, {Susan J.} and Kuchenbaecker, {Karoline B.} and Penny Soucy and Jonathan Beesley and Xiaoqing Chen and Xianshu Wang and Tomas Kirchhoff and Lesley McGuffog and Daniel Barrowdale and Andrew Lee and Sue Healey and Sinilnikova, {Olga M.} and Andrulis, {Irene L.} and Hilmi Ozcelik and Mulligan, {Anna Marie} and Mads Thomassen 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 Gisela Barbany-Bustinza and Niklas Loman and Maria Soller and Hans Ehrencrona and Per Karlsson and Katherine Nathanson and Rebbeck, {Timothy R.} and Domchek, {Susan M.} and Ania Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Elzbieta Zołwocka and Tomasz Huzarski and Tomasz Byrski and Jacek Gronwald and Cezary Cybulski and Bohdan Goŕski and Ana Osorio and Mercedes Durań and Tejada, {Mar{\'i}a Isabel} and Javier Benitez and Ute Hamann and Hogervorst, {Frans B L} and {Van Os}, {Theo A.} and {Van Leeuwen}, {Flora E.} and Meijers-Heijboer, {Hanne E J} and Juul Wijnen and Blok, {Marinus J.} and Marleen Kets and Hooning, {Maartje J.} and Oldenburg, {Rogier A.} and Ausems, {Margreet G E M} and Susan Peock and Debra Frost and Ellis, {Steve D.} and Radka Platte and Elena Fineberg and Evans, {D. Gareth} and Chris Jacobs and Eeles, {Rosalind A.} and Julian Adlard and Rosemarie Davidson and Eccles, {Diana M.} and Trevor Cole and Jackie Cook and Joan Paterson and Carole Brewer and Fiona Douglas and Hodgson, {Shirley V.} and Morrison, {Patrick J.} and Lisa Walker and Porteous, {Mary E.} and Kennedy, {M. John} and Side, {Lucy E.} and Betsy Bove and Godwin, {Andrew K.} and Dominique Stoppa-Lyonnet and Marion Fassy-Colcombet and Laurent Castera and Franco̧is Cornelis and Sylvie Mazoyer and Meĺanie Le{\'o}ne and Nadia Boutry-Kryza and {Bressac-de Paillerets}, Brigitte and Olivier Caron and Pascal Pujol and Isabelle Coupier and Capucine Delnatte and Linda Akloul and Lynch, {Henry T.} and Snyder, {Carrie L.} and Buys, {Saundra S.} and Daly, {Mary B.} and Terry, {Mary Beth} and Chung, {Wendy K.} and John, {Esther M.} and Alexander Miron and Southey, {Melissa C.} and Hopper, {John L.} and Goldgar, {David E.} and Singer, {Christian F.} and Christine Rappaport and Tea, {Muy Kheng M} and Anneliese Fink-Retter and Hansen, {Thomas V O} and Nielsen, {Finn C.} and Aoalgeir Arason and Joseph Vijai and Sohela Shah and Kara Sarrel and Robson, {Mark E.} and Marion Piedmonte and Kelly Phillips and Jack Basil and Rubinstein, {Wendy S.} and John Boggess and Katie Wakeley and Amanda Ewart-Toland and Marco Montagna and Simona Agata and Imyanitov, {Evgeny N.} and Claudine Isaacs and Ramunas Janavicius and Conxi Lazaro and Ignacio Blanco and Lidia Feliubadalo and Joan Brunet and Gayther, {Simon A.} and Pharoah, {Paul P D} and Odunsi, {Kunle O.} and Karlan, {Beth Y.} and Walsh, {Christine S.} and Edith Olah and Teo, {Soo Hwang} and Ganz, {Patricia A.} and Beattie, {Mary S.} and {Van Rensburg}, {Elizabeth J.} and Dorfling, {Cecelia M.} and Orland Diez and Ava Kwong and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Simone Heidemann and Dieter Niederacher and Sabine Preisler-Adams and Dorothea Gadzicki and Raymonda Varon-Mateeva and Helmut Deissler and Andrea Gehrig and Christian Sutter and Karin Kast and Britta Fiebig and Wolfram Heinritz and Trinidad Caldes and {De La Hoya}, Miguel and Muranen, {Taru A.} and Heli Nevanlinna and Tischkowitz, {Marc D.} and Spurdle, {Amanda B.} and Neuhausen, {Susan L.} and Ding, {Yuan Chun} and Lindor, {Noralane M.} and Zachary Fredericksen and Pankratz, {V. Shane} and Paolo Peterlongo and Siranoush Manoukian and Bernard Peissel and Daniela Zaffaroni and Monica Barile and Loris Bernard and Alessandra Viel and Giuseppe Giannini and Liliana Varesco and Paolo Radice and Greene, {Mark H.} and Mai, {Phuong L.} and Easton, {Douglas F.} and Georgia Chenevix-Trench and Kenneth Offit and Jacques Simard",
year = "2012",
month = "4",
doi = "10.1158/1055-9965.EPI-11-0888",
language = "English",
volume = "21",
pages = "645--657",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - 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

AU - Couch, Fergus J.

AU - Gaudet, Mia M.

AU - Antoniou, Antonis C.

AU - Ramus, Susan J.

AU - Kuchenbaecker, Karoline B.

AU - Soucy, Penny

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Wang, Xianshu

AU - Kirchhoff, Tomas

AU - McGuffog, Lesley

AU - Barrowdale, Daniel

AU - Lee, Andrew

AU - Healey, Sue

AU - Sinilnikova, Olga M.

AU - Andrulis, Irene L.

AU - Ozcelik, Hilmi

AU - Mulligan, Anna Marie

AU - Thomassen, Mads

AU - Gerdes, Anne Marie

AU - Jensen, Uffe Birk

AU - Skytte, Anne Bine

AU - Kruse, Torben A.

AU - Caligo, Maria A.

AU - Von Wachenfeldt, Anna

AU - Barbany-Bustinza, Gisela

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AU - Karlsson, Per

AU - Nathanson, Katherine

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AU - Domchek, Susan M.

AU - Jakubowska, Ania

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Zołwocka, Elzbieta

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AU - Byrski, Tomasz

AU - Gronwald, Jacek

AU - Cybulski, Cezary

AU - Goŕski, Bohdan

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AU - Durań, Mercedes

AU - Tejada, María Isabel

AU - Benitez, Javier

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AU - Peock, Susan

AU - Frost, Debra

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AU - Preisler-Adams, Sabine

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AU - Varon-Mateeva, Raymonda

AU - Deissler, Helmut

AU - Gehrig, Andrea

AU - Sutter, Christian

AU - Kast, Karin

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AU - Heinritz, Wolfram

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AU - De La Hoya, Miguel

AU - Muranen, Taru A.

AU - Nevanlinna, Heli

AU - Tischkowitz, Marc D.

AU - Spurdle, Amanda B.

AU - Neuhausen, Susan L.

AU - Ding, Yuan Chun

AU - Lindor, Noralane M.

AU - Fredericksen, Zachary

AU - Pankratz, V. Shane

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Zaffaroni, Daniela

AU - Barile, Monica

AU - Bernard, Loris

AU - Viel, Alessandra

AU - Giannini, Giuseppe

AU - Varesco, Liliana

AU - Radice, Paolo

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Easton, Douglas F.

AU - Chenevix-Trench, Georgia

AU - Offit, Kenneth

AU - Simard, Jacques

PY - 2012/4

Y1 - 2012/4

N2 - 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.Wealso 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.

AB - 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.Wealso 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.

UR - http://www.scopus.com/inward/record.url?scp=84859377440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859377440&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-11-0888

DO - 10.1158/1055-9965.EPI-11-0888

M3 - Article

C2 - 22351618

AN - SCOPUS:84859377440

VL - 21

SP - 645

EP - 657

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 4

ER -