Abstract
In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
| Original language | English |
|---|---|
| Article number | 9688 |
| Number of pages | 14 |
| Journal | Scientific Reports |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 16 Jun 2020 |
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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. / Liu, Jingjing; Prager-van der Smissen, Wendy J.C.; Collée, J. Margriet; Bolla, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Ahearn, Thomas U.; Aittomäki, Kristiina; Ambrosone, Christine B.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Arnold, Norbert; Aronson, Kristan J.; Augustinsson, Annelie; Auvinen, Päivi; Becher, Heiko; Beckmann, Matthias W.; Behrens, Sabine; Bermisheva, Marina; Bernstein, Leslie; Bogdanova, Natalia V.; Bogdanova-Markov, Nadja; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Briceno, Ignacio; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Cai, Qiuyin; Cai, Hui; Campa, Daniele; Canzian, Federico; Castelao, Jose E.; Chang-Claude, Jenny; Chanock, Stephen J.; Choi, Ji Yeob; Christiaens, Melissa; Clarke, Christine L.; Couch, Fergus J.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Dos-Santos-Silva, Isabel; Dwek, Miriam; Eccles, Diana M.; Eliassen, A. Heather; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; Fritschi, Lin; Gago-Dominguez, Manuela; Gapstur, Susan M.; García-Closas, Montserrat; García-Sáenz, José A.; Gaudet, Mia M.; Giles, Graham G.; Goldberg, Mark S.; Goldgar, David E.; Guénel, Pascal; Haiman, Christopher A.; Håkansson, Niclas; Hall, Per; Harrington, Patricia A.; Hart, Steven N.; Hartman, Mikael; Hillemanns, Peter; Hopper, John L.; Hou, Ming Feng; Hunter, David J.; Huo, Dezheng; Ito, Hidemi; Iwasaki, Motoki; Jakimovska, Milena; Jakubowska, Anna; John, Esther M.; Kaaks, Rudolf; Kang, Daehee; Keeman, Renske; Khusnutdinova, Elza; Kim, Sung Won; Kraft, Peter; Kristensen, Vessela N.; Kurian, Allison W.; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert N.; Lubiński, Jan; Mannermaa, Arto; Manoochehri, Mehdi; Manoukian, Siranoush; Margolin, Sara; Mariapun, Shivaani; Matsuo, Keitaro; Maurer, Tabea; Mavroudis, Dimitrios; Meindl, Alfons; Menon, Usha; Milne, Roger L.; Muir, Kenneth; Mulligan, Anna Marie; Neuhausen, Susan L.; Nevanlinna, Heli; Offit, Kenneth; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Orr, Nick; Park, Sue K.; Peterlongo, Paolo; Peto, Julian; Plaseska-Karanfilska, Dijana; Presneau, Nadege; Rack, Brigitte; Rau-Murthy, Rohini; Rennert, Gad; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Ruebner, Matthias; Saloustros, Emmanouil; Schmutzler, Rita K.; Schneeweiss, Andreas; Scott, Christopher; Shah, Mitul; Shen, Chen Yang; Shu, Xiao Ou; Simard, Jacques; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Tamimi, Rulla M.; Tapper, William J.; Teo, Soo H.; Terry, Mary Beth; Torres, Diana; Truong, Thérèse; Untch, Michael; Vachon, Celine M.; van Asperen, Christi J.; Wolk, Alicja; Yamaji, Taiki; Zheng, Wei; Ziogas, Argyrios; Ziv, Elad; Torres-Mejía, Gabriela; Dörk, Thilo; Swerdlow, Anthony J.; Hamann, Ute; Schmidt, Marjanka K.; Dunning, Alison M.; Pharoah, Paul D.P.; Easton, Douglas F.; Hooning, Maartje J.; Martens, John W.M.; Hollestelle, Antoinette; NBCS Collaborators; ABCTB Investigators.
In: Scientific Reports, Vol. 10, No. 1, 9688, 16.06.2020.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
AU - Liu, Jingjing
AU - Prager-van der Smissen, Wendy J.C.
AU - Collée, J. Margriet
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Michailidou, Kyriaki
AU - Dennis, Joe
AU - Ahearn, Thomas U.
AU - Aittomäki, Kristiina
AU - Ambrosone, Christine B.
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia N.
AU - Arndt, Volker
AU - Arnold, Norbert
AU - Aronson, Kristan J.
AU - Augustinsson, Annelie
AU - Auvinen, Päivi
AU - Becher, Heiko
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - Bernstein, Leslie
AU - Bogdanova, Natalia V.
AU - Bogdanova-Markov, Nadja
AU - Bojesen, Stig E.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Briceno, Ignacio
AU - Brucker, Sara Y.
AU - Brüning, Thomas
AU - Burwinkel, Barbara
AU - Cai, Qiuyin
AU - Cai, Hui
AU - Campa, Daniele
AU - Canzian, Federico
AU - Castelao, Jose E.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Choi, Ji Yeob
AU - Christiaens, Melissa
AU - Clarke, Christine L.
AU - Couch, Fergus J.
AU - Czene, Kamila
AU - Daly, Mary B.
AU - Devilee, Peter
AU - Dos-Santos-Silva, Isabel
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Eliassen, A. Heather
AU - Fasching, Peter A.
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Fritschi, Lin
AU - Gago-Dominguez, Manuela
AU - Gapstur, Susan M.
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Gaudet, Mia M.
AU - Giles, Graham G.
AU - Goldberg, Mark S.
AU - Goldgar, David E.
AU - Guénel, Pascal
AU - Haiman, Christopher A.
AU - Håkansson, Niclas
AU - Hall, Per
AU - Harrington, Patricia A.
AU - Hart, Steven N.
AU - Hartman, Mikael
AU - Hillemanns, Peter
AU - Hopper, John L.
AU - Hou, Ming Feng
AU - Hunter, David J.
AU - Huo, Dezheng
AU - Ito, Hidemi
AU - Iwasaki, Motoki
AU - Jakimovska, Milena
AU - Jakubowska, Anna
AU - John, Esther M.
AU - Kaaks, Rudolf
AU - Kang, Daehee
AU - Keeman, Renske
AU - Khusnutdinova, Elza
AU - Kim, Sung Won
AU - Kraft, Peter
AU - Kristensen, Vessela N.
AU - Kurian, Allison W.
AU - Le Marchand, Loic
AU - Li, Jingmei
AU - Lindblom, Annika
AU - Lophatananon, Artitaya
AU - Luben, Robert N.
AU - Lubiński, Jan
AU - Mannermaa, Arto
AU - Manoochehri, Mehdi
AU - Manoukian, Siranoush
AU - Margolin, Sara
AU - Mariapun, Shivaani
AU - Matsuo, Keitaro
AU - Maurer, Tabea
AU - Mavroudis, Dimitrios
AU - Meindl, Alfons
AU - Menon, Usha
AU - Milne, Roger L.
AU - Muir, Kenneth
AU - Mulligan, Anna Marie
AU - Neuhausen, Susan L.
AU - Nevanlinna, Heli
AU - Offit, Kenneth
AU - Olopade, Olufunmilayo I.
AU - Olson, Janet E.
AU - Olsson, Håkan
AU - Orr, Nick
AU - Park, Sue K.
AU - Peterlongo, Paolo
AU - Peto, Julian
AU - Plaseska-Karanfilska, Dijana
AU - Presneau, Nadege
AU - Rack, Brigitte
AU - Rau-Murthy, Rohini
AU - Rennert, Gad
AU - Rennert, Hedy S.
AU - Rhenius, Valerie
AU - Romero, Atocha
AU - Ruebner, Matthias
AU - Saloustros, Emmanouil
AU - Schmutzler, Rita K.
AU - Schneeweiss, Andreas
AU - Scott, Christopher
AU - Shah, Mitul
AU - Shen, Chen Yang
AU - Shu, Xiao Ou
AU - Simard, Jacques
AU - Sohn, Christof
AU - Southey, Melissa C.
AU - Spinelli, John J.
AU - Tamimi, Rulla M.
AU - Tapper, William J.
AU - Teo, Soo H.
AU - Terry, Mary Beth
AU - Torres, Diana
AU - Truong, Thérèse
AU - Untch, Michael
AU - Vachon, Celine M.
AU - van Asperen, Christi J.
AU - Wolk, Alicja
AU - Yamaji, Taiki
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Ziv, Elad
AU - Torres-Mejía, Gabriela
AU - Dörk, Thilo
AU - Swerdlow, Anthony J.
AU - Hamann, Ute
AU - Schmidt, Marjanka K.
AU - Dunning, Alison M.
AU - Pharoah, Paul D.P.
AU - Easton, Douglas F.
AU - Hooning, Maartje J.
AU - Martens, John W.M.
AU - Hollestelle, Antoinette
AU - NBCS Collaborators
AU - ABCTB Investigators
PY - 2020/6/16
Y1 - 2020/6/16
N2 - In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
AB - In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
UR - http://www.scopus.com/inward/record.url?scp=85086686420&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-65665-y
DO - 10.1038/s41598-020-65665-y
M3 - Article
C2 - 32546843
AN - SCOPUS:85086686420
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9688
ER -