Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

NBCS Collaborators; Jingjing Liu; Wendy J C Prager-van der Smissen; J Margriet Collée; Manjeet K Bolla; Qin Wang; Kyriaki Michailidou; Joe Dennis; Thomas U Ahearn; Kristiina Aittomäki; Christine B Ambrosone; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Volker Arndt; Norbert Arnold; Kristan J Aronson; Annelie Augustinsson; Päivi Auvinen; Heiko Becher; Matthias W Beckmann; Sabine Behrens; Marina Bermisheva; Leslie Bernstein; Natalia V Bogdanova; Nadja Bogdanova-Markov; Stig E Bojesen; Hiltrud Brauch; Hermann Brenner; Ignacio Briceno; Sara Y Brucker; Thomas Brüning; Barbara Burwinkel; Qiuyin Cai; Hui Cai; Daniele Campa; Federico Canzian; Jose E Castelao; Jenny Chang-Claude; Stephen J Chanock; Ji-Yeob Choi; Melissa Christiaens; Christine L Clarke; Fergus J Couch; Kamila Czene; Mary B Daly; Peter Devilee; Isabel Dos-Santos-Silva; Miriam Dwek; Diana M Eccles; A Heather Eliassen

doi:10.1038/s41598-020-65665-y

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

NBCS Collaborators, Jingjing Liu, Wendy J C Prager-van der Smissen, J Margriet Collée, Manjeet K Bolla, Qin Wang, Kyriaki Michailidou, Joe Dennis, Thomas U Ahearn, Kristiina Aittomäki, Christine B Ambrosone, Irene L Andrulis, Hoda Anton-Culver, Natalia N Antonenkova, Volker Arndt, Norbert Arnold, Kristan J Aronson, Annelie Augustinsson, Päivi Auvinen, Heiko BecherMatthias W Beckmann, Sabine Behrens, Marina Bermisheva, Leslie Bernstein, Natalia V Bogdanova, Nadja Bogdanova-Markov, Stig E Bojesen, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Sara Y Brucker, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Hui Cai, Daniele Campa, Federico Canzian, Jose E Castelao, Jenny Chang-Claude, Stephen J Chanock, Ji-Yeob Choi, Melissa Christiaens, Christine L Clarke, Fergus J Couch, Kamila Czene, Mary B Daly, Peter Devilee, Isabel Dos-Santos-Silva, Miriam Dwek, Diana M Eccles, A Heather Eliassen

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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
Pages (from-to)	9688
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-65665-y
State	Published - May 16 2020

Keywords

Breast Neoplasms/genetics
Female
Genetic Predisposition to Disease/genetics
Genotyping Techniques
Germ-Line Mutation/genetics
Homeodomain Proteins/genetics
Humans
Middle Aged
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-020-65665-y

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NBCS Collaborators, Liu, J., Prager-van der Smissen, W. J. C., Collée, J. M., Bolla, M. K., Wang, Q., Michailidou, K., Dennis, J., Ahearn, T. U., Aittomäki, K., Ambrosone, C. B., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Augustinsson, A., Auvinen, P., ... Eliassen, A. H. (2020). Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. Scientific Reports, 10(1), 9688. Article 9688. https://doi.org/10.1038/s41598-020-65665-y

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title = "Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk",

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.",

keywords = "Breast Neoplasms/genetics, Female, Genetic Predisposition to Disease/genetics, Genotyping Techniques, Germ-Line Mutation/genetics, Homeodomain Proteins/genetics, Humans, Middle Aged, Risk Factors",

author = "{NBCS Collaborators} and Jingjing Liu and {Prager-van der Smissen}, {Wendy J C} and Coll{\'e}e, {J Margriet} and Bolla, {Manjeet K} and Qin Wang and Kyriaki Michailidou and Joe Dennis and Ahearn, {Thomas U} and Kristiina Aittom{\"a}ki and Ambrosone, {Christine B} and Andrulis, {Irene L} and Hoda Anton-Culver and Antonenkova, {Natalia N} and Volker Arndt and Norbert Arnold and Aronson, {Kristan J} and Annelie Augustinsson and P{\"a}ivi Auvinen and Heiko Becher and Beckmann, {Matthias W} and Sabine Behrens and Marina Bermisheva and Leslie Bernstein and Bogdanova, {Natalia V} and Nadja Bogdanova-Markov and Bojesen, {Stig E} and Hiltrud Brauch and Hermann Brenner and Ignacio Briceno and Brucker, {Sara Y} and Thomas Br{\"u}ning and Barbara Burwinkel and Qiuyin Cai and Hui Cai and Daniele Campa and Federico Canzian and Castelao, {Jose E} and Jenny Chang-Claude and Chanock, {Stephen J} and Ji-Yeob Choi and Melissa Christiaens and Clarke, {Christine L} and Couch, {Fergus J} and Kamila Czene and Daly, {Mary B} and Peter Devilee and Isabel Dos-Santos-Silva and Miriam Dwek and Eccles, {Diana M} and Eliassen, {A Heather}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = may,

day = "16",

doi = "10.1038/s41598-020-65665-y",

language = "English",

volume = "10",

pages = "9688",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

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NBCS Collaborators, Liu, J, Prager-van der Smissen, WJC, Collée, JM, Bolla, MK, Wang, Q, Michailidou, K, Dennis, J, Ahearn, TU, Aittomäki, K, Ambrosone, CB, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Arnold, N, Aronson, KJ, Augustinsson, A, Auvinen, P, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Bernstein, L, Bogdanova, NV, Bogdanova-Markov, N, Bojesen, SE, Brauch, H, Brenner, H, Briceno, I, Brucker, SY, Brüning, T, Burwinkel, B, Cai, Q, Cai, H, Campa, D, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Christiaens, M, Clarke, CL, Couch, FJ, Czene, K, Daly, MB, Devilee, P, Dos-Santos-Silva, I, Dwek, M, Eccles, DM & Eliassen, AH 2020, 'Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk', Scientific Reports, vol. 10, no. 1, 9688, pp. 9688. https://doi.org/10.1038/s41598-020-65665-y

TY - JOUR

T1 - Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

AU - NBCS Collaborators

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

PY - 2020/5/16

Y1 - 2020/5/16

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.

KW - Breast Neoplasms/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genotyping Techniques

KW - Germ-Line Mutation/genetics

KW - Homeodomain Proteins/genetics

KW - Humans

KW - Middle Aged

KW - Risk Factors

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

SN - 2045-2322

VL - 10

SP - 9688

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 9688

ER -

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Abstract

Keywords

UN SDGs

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