Height and breast cancer risk: Evidence from prospective studies and mendelian randomization

Ben Shan Zhang; Xiao-Ou Shu; Ryan J. Delahanty; Chenjie Zeng; Kyriaki Michailidou; Manjeet K. Bolla; Qin Wang; Joe Dennis; Wanqing Wen; Jirong Long; Chun Li; Alison M Dunning; Jenny Chang-Claude; Mitul Shah; Barbara J. Perkins; Kamila Czene; Hatef Darabi; Mikael Eriksson; Stig E Bojesen; Børge G. Nordestgaard; Sune F Nielsen; Henrik Flyger; Diether Lambrechts; Patrick Neven; Hans Wildiers; Giuseppe Floris; Marjanka K. Schmidt; Matti A. Rookus; Katja Van Den Hurk; Wim L.A.M. De Kort; Fergus J Couch; Janet E Olson; Emily Hallberg; Celine M Vachon; Anja Rudolph; Petra Seibold; Dieter Flesch-Janys; Julian Peto; Isabel Dos-Santos-Silva; Olivia Fletcher; Nichola Johnson; Heli Nevanlinna; Taru A. Muranen; Kristiina Aittomäki; Carl Blomqvist; Jingmei Li; Keith Humphreys; Judith S. Brand; Pascal Guénel; Thérèse Truong; Emilie Cordina-Duverger; Florence Menegaux; Barbara Burwinkel; Frederik Marme; Rongxi Yang; Harald Surowy; Javier Benitez; Pilar M. Zamora; Jose Ignacio Arias Perez; Angela Cox; Simon S Cross; Malcolm W R Reed; Irene L Andrulis; Julia A Knight; Gord Glendon; Sandrine Tchatchou; Elinor J Sawyer; Ian P Tomlinson; Michael J. Kerin; Nicola Miller; Georgia Chenevix-Trench; Christopher A Haiman; Brian E Henderson; Fredrick Schumacher; Loic Le Marchand; Annika Lindblom; Sara Margolin; Maartje J Hooning; John W M Martens; Madeleine M A Tilanus-Linthorst; J. Margriet Collée; John L. Hopper; Melissa C. Southey; Helen Tsimiklis; Carmel Apicella; Susan Slager; Amanda E. Toland; Christine B. Ambrosone; Drakoulis Yannoukakos; Graham G. Giles; Roger L. Milne; Catriona McLean; Peter A. Fasching; Lothar Haeberle; Arif B Ekici; Matthias W. Beckmann; Hermann Brenner; Aida Karina Dieffenbach; Volker Arndt; Christa Stegmaier; Anthony J Swerdlow; Alan Ashworth; Nick Orr; Michael Jones; Jonine D Figueroa; Montserrat Garcia-Closas; Louise Brinton; Jolanta Lissowska; Martine Dumont; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Hiltrud Brauch; Thomas Brüning; Yon-Dschun Ko; Paolo Peterlongo; Siranoush Manoukian; Bernardo Bonanni; Paolo Radice; Natalia Bogdanova; Natalia Antonenkova; Thilo Dörk; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M. Hartikainen; Peter Devilee; Caroline Seynaeve; Christi J. Van Asperen; Anna Jakubowska; Jan Lubiski; Katarzyna Jaworska-Bieniek; Katarzyna Durda; Ute Hamann; Diana Torres; Rita K. Schmutzler; Susan L Neuhausen; Hoda Anton-Culver; Vessela N. Kristensen; Grethe I. Grenaker Alnæs; Brandon L. Pierce; Peter Kraft; Ulrike Peters; Sara Lindstrom; Daniela Seminara; Stephen Burgess; Habibul Ahsan; Alice S Whittemore; Esther M. John; Marilie D. Gammon; Kathleen E. Malone; Daniel C. Tessier; Daniel Vincent; Francois Bacot; Craig Luccarini; Caroline Baynes; Shahana Ahmed; Mel J. Maranian; Catherine S. Healey; Anna González-Neira; Guillermo Pita; M. Rosario Alonso; Nuria Álvarez; Daniel Herrero; Paul D P Pharoah; Jacques Simard; Per Hall; David J. Hunter; Douglas F Easton; Wei Zheng; the DRIVE Project; kConFab Investigators; Australian Ovarian study group; The GENICA Network

doi:10.1093/jnci/djv219

Height and breast cancer risk: Evidence from prospective studies and mendelian randomization

Ben Shan Zhang, Xiao-Ou Shu, Ryan J. Delahanty, Chenjie Zeng, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe Dennis, Wanqing Wen, Jirong Long, Chun Li, Alison M Dunning, Jenny Chang-Claude, Mitul Shah, Barbara J. Perkins, Kamila Czene, Hatef Darabi, Mikael Eriksson, Stig E Bojesen, Børge G. NordestgaardSune F Nielsen, Henrik Flyger, Diether Lambrechts, Patrick Neven, Hans Wildiers, Giuseppe Floris, Marjanka K. Schmidt, Matti A. Rookus, Katja Van Den Hurk, Wim L.A.M. De Kort, Fergus J Couch, Janet E Olson, Emily Hallberg, Celine M Vachon, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Julian Peto, Isabel Dos-Santos-Silva, Olivia Fletcher, Nichola Johnson, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Jingmei Li, Keith Humphreys, Judith S. Brand, Pascal Guénel, Thérèse Truong, Emilie Cordina-Duverger, Florence Menegaux, Barbara Burwinkel, Frederik Marme, Rongxi Yang, Harald Surowy, Javier Benitez, Pilar M. Zamora, Jose Ignacio Arias Perez, Angela Cox, Simon S Cross, Malcolm W R Reed, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Elinor J Sawyer, Ian P Tomlinson, Michael J. Kerin, Nicola Miller, Georgia Chenevix-Trench, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Annika Lindblom, Sara Margolin, Maartje J Hooning, John W M Martens, Madeleine M A Tilanus-Linthorst, J. Margriet Collée, John L. Hopper, Melissa C. Southey, Helen Tsimiklis, Carmel Apicella, Susan Slager, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Graham G. Giles, Roger L. Milne, Catriona McLean, Peter A. Fasching, Lothar Haeberle, Arif B Ekici, Matthias W. Beckmann, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony J Swerdlow, Alan Ashworth, Nick Orr, Michael Jones, Jonine D Figueroa, Montserrat Garcia-Closas, Louise Brinton, Jolanta Lissowska, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Ko, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Paolo Radice, Natalia Bogdanova, Natalia Antonenkova, Thilo Dörk, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M. Hartikainen, Peter Devilee, Caroline Seynaeve, Christi J. Van Asperen, Anna Jakubowska, Jan Lubiski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Ute Hamann, Diana Torres, Rita K. Schmutzler, Susan L Neuhausen, Hoda Anton-Culver, Vessela N. Kristensen, Grethe I. Grenaker Alnæs, Brandon L. Pierce, Peter Kraft, Ulrike Peters, Sara Lindstrom, Daniela Seminara, Stephen Burgess, Habibul Ahsan, Alice S Whittemore, Esther M. John, Marilie D. Gammon, Kathleen E. Malone, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel J. Maranian, Catherine S. Healey, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Nuria Álvarez, Daniel Herrero, Paul D P Pharoah, Jacques Simard, Per Hall, David J. Hunter, Douglas F Easton, Wei Zheng, the DRIVE Project, kConFab Investigators, Australian Ovarian study group, The GENICA Network

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

107 Citations (Scopus)

Abstract

Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5 216 302 women, including 113 178 events. In a consortium with individual-level data from 46 325 case patients and 42 482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16 003 case patients and 41 335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10 cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10 cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5 × 10-8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.

Original language	English
Article number	djv219
Number of pages	17
Journal	Journal of the National Cancer Institute
Volume	107
Issue number	11
DOIs	https://doi.org/10.1093/jnci/djv219
Publication status	Published - Nov 2015
Externally published	Yes

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

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10.1093/jnci/djv219

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Cite this

Zhang, B. S., Shu, X.-O., Delahanty, R. J., Zeng, C., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Wen, W., Long, J., Li, C., Dunning, A. M., Chang-Claude, J., Shah, M., Perkins, B. J., Czene, K., Darabi, H., Eriksson, M., Bojesen, S. E., ... The GENICA Network (2015). Height and breast cancer risk: Evidence from prospective studies and mendelian randomization. Journal of the National Cancer Institute, 107(11), Article djv219. https://doi.org/10.1093/jnci/djv219

@article{df60cd7d261b46c4a8b7b5f5eee23553,

title = "Height and breast cancer risk: Evidence from prospective studies and mendelian randomization",

abstract = "Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5 216 302 women, including 113 178 events. In a consortium with individual-level data from 46 325 case patients and 42 482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16 003 case patients and 41 335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10 cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10 cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5 × 10-8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.",

author = "Zhang, {Ben Shan} and Xiao-Ou Shu and Delahanty, {Ryan J.} and Chenjie Zeng and Kyriaki Michailidou and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Wanqing Wen and Jirong Long and Chun Li and Dunning, {Alison M} and Jenny Chang-Claude and Mitul Shah and Perkins, {Barbara J.} and Kamila Czene and Hatef Darabi and Mikael Eriksson and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F} and Henrik Flyger and Diether Lambrechts and Patrick Neven and Hans Wildiers and Giuseppe Floris and Schmidt, {Marjanka K.} and Rookus, {Matti A.} and {Van Den Hurk}, Katja and {De Kort}, {Wim L.A.M.} and Couch, {Fergus J} and Olson, {Janet E} and Emily Hallberg and Vachon, {Celine M} and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Julian Peto and Isabel Dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Heli Nevanlinna and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Jingmei Li and Keith Humphreys and Brand, {Judith S.} and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Emilie Cordina-Duverger and Florence Menegaux and Barbara Burwinkel and Frederik Marme and Rongxi Yang and Harald Surowy and Javier Benitez and Zamora, {Pilar M.} and Perez, {Jose Ignacio Arias} and Angela Cox and Cross, {Simon S} and Reed, {Malcolm W R} and Andrulis, {Irene L} and Knight, {Julia A} and Gord Glendon and Sandrine Tchatchou and Sawyer, {Elinor J} and Tomlinson, {Ian P} and Kerin, {Michael J.} and Nicola Miller and Georgia Chenevix-Trench and Haiman, {Christopher A} and Henderson, {Brian E} and Fredrick Schumacher and {Le Marchand}, Loic and Annika Lindblom and Sara Margolin and Hooning, {Maartje J} and Martens, {John W M} and Tilanus-Linthorst, {Madeleine M A} and Coll{\'e}e, {J. Margriet} and Hopper, {John L.} and Southey, {Melissa C.} and Helen Tsimiklis and Carmel Apicella and Susan Slager and Toland, {Amanda E.} and Ambrosone, {Christine B.} and Drakoulis Yannoukakos and Giles, {Graham G.} and Milne, {Roger L.} and Catriona McLean and Fasching, {Peter A.} and Lothar Haeberle and Ekici, {Arif B} and Beckmann, {Matthias W.} and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Swerdlow, {Anthony J} and Alan Ashworth and Nick Orr and Michael Jones and Figueroa, {Jonine D} and Montserrat Garcia-Closas and Louise Brinton and Jolanta Lissowska and Martine Dumont and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Hiltrud Brauch and Thomas Br{\"u}ning and Yon-Dschun Ko and Paolo Peterlongo and Siranoush Manoukian and Bernardo Bonanni and Paolo Radice and Natalia Bogdanova and Natalia Antonenkova and Thilo D{\"o}rk and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M.} and Peter Devilee and Caroline Seynaeve and {Van Asperen}, {Christi J.} and Anna Jakubowska and Jan Lubiski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Ute Hamann and Diana Torres and Schmutzler, {Rita K.} and Neuhausen, {Susan L} and Hoda Anton-Culver and Kristensen, {Vessela N.} and {Grenaker Aln{\ae}s}, {Grethe I.} and Pierce, {Brandon L.} and Peter Kraft and Ulrike Peters and Sara Lindstrom and Daniela Seminara and Stephen Burgess and Habibul Ahsan and Whittemore, {Alice S} and John, {Esther M.} and Gammon, {Marilie D.} and Malone, {Kathleen E.} and Tessier, {Daniel C.} and Daniel Vincent and Francois Bacot and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Maranian, {Mel J.} and Healey, {Catherine S.} and Anna Gonz{\'a}lez-Neira and Guillermo Pita and Alonso, {M. Rosario} and Nuria {\'A}lvarez and Daniel Herrero and Pharoah, {Paul D P} and Jacques Simard and Per Hall and Hunter, {David J.} and Easton, {Douglas F} and Wei Zheng and {the DRIVE Project} and {kConFab Investigators} and {Australian Ovarian study group} and {The GENICA Network}",

year = "2015",

month = nov,

doi = "10.1093/jnci/djv219",

language = "English",

volume = "107",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "11",

}

Zhang, BS, Shu, X-O, Delahanty, RJ, Zeng, C, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Wen, W, Long, J, Li, C, Dunning, AM, Chang-Claude, J, Shah, M, Perkins, BJ, Czene, K, Darabi, H, Eriksson, M, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Lambrechts, D, Neven, P, Wildiers, H, Floris, G, Schmidt, MK, Rookus, MA, Van Den Hurk, K, De Kort, WLAM, Couch, FJ, Olson, JE, Hallberg, E, Vachon, CM, Rudolph, A, Seibold, P, Flesch-Janys, D, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Li, J, Humphreys, K, Brand, JS, Guénel, P, Truong, T, Cordina-Duverger, E, Menegaux, F, Burwinkel, B, Marme, F, Yang, R, Surowy, H, Benitez, J, Zamora, PM, Perez, JIA, Cox, A, Cross, SS, Reed, MWR, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Sawyer, EJ, Tomlinson, IP, Kerin, MJ, Miller, N, Chenevix-Trench, G, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Lindblom, A, Margolin, S, Hooning, MJ, Martens, JWM, Tilanus-Linthorst, MMA, Collée, JM, Hopper, JL, Southey, MC, Tsimiklis, H, Apicella, C, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Giles, GG, Milne, RL, McLean, C, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Swerdlow, AJ, Ashworth, A, Orr, N, Jones, M, Figueroa, JD, Garcia-Closas, M, Brinton, L, Lissowska, J, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Brauch, H, Brüning, T, Ko, Y-D, Peterlongo, P, Manoukian, S, Bonanni, B, Radice, P, Bogdanova, N, Antonenkova, N, Dörk, T, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Devilee, P, Seynaeve, C, Van Asperen, CJ, Jakubowska, A, Lubiski, J, Jaworska-Bieniek, K, Durda, K, Hamann, U, Torres, D, Schmutzler, RK, Neuhausen, SL, Anton-Culver, H, Kristensen, VN, Grenaker Alnæs, GI, Pierce, BL, Kraft, P, Peters, U, Lindstrom, S, Seminara, D, Burgess, S, Ahsan, H, Whittemore, AS, John, EM, Gammon, MD, Malone, KE, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Ahmed, S, Maranian, MJ, Healey, CS, González-Neira, A, Pita, G, Alonso, MR, Álvarez, N, Herrero, D, Pharoah, PDP, Simard, J, Hall, P, Hunter, DJ, Easton, DF, Zheng, W, the DRIVE Project, kConFab Investigators, Australian Ovarian study group & The GENICA Network 2015, 'Height and breast cancer risk: Evidence from prospective studies and mendelian randomization', Journal of the National Cancer Institute, vol. 107, no. 11, djv219. https://doi.org/10.1093/jnci/djv219

TY - JOUR

T1 - Height and breast cancer risk

T2 - Evidence from prospective studies and mendelian randomization

AU - Zhang, Ben Shan

AU - Shu, Xiao-Ou

AU - Delahanty, Ryan J.

AU - Zeng, Chenjie

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Wen, Wanqing

AU - Long, Jirong

AU - Li, Chun

AU - Dunning, Alison M

AU - Chang-Claude, Jenny

AU - Shah, Mitul

AU - Perkins, Barbara J.

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - Lambrechts, Diether

AU - Neven, Patrick

AU - Wildiers, Hans

AU - Floris, Giuseppe

AU - Schmidt, Marjanka K.

AU - Rookus, Matti A.

AU - Van Den Hurk, Katja

AU - De Kort, Wim L.A.M.

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Hallberg, Emily

AU - Vachon, Celine M

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Nevanlinna, Heli

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Li, Jingmei

AU - Humphreys, Keith

AU - Brand, Judith S.

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Cordina-Duverger, Emilie

AU - Menegaux, Florence

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Yang, Rongxi

AU - Surowy, Harald

AU - Benitez, Javier

AU - Zamora, Pilar M.

AU - Perez, Jose Ignacio Arias

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm W R

AU - Andrulis, Irene L

AU - Knight, Julia A

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Sawyer, Elinor J

AU - Tomlinson, Ian P

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Chenevix-Trench, Georgia

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Hooning, Maartje J

AU - Martens, John W M

AU - Tilanus-Linthorst, Madeleine M A

AU - Collée, J. Margriet

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Tsimiklis, Helen

AU - Apicella, Carmel

AU - Slager, Susan

AU - Toland, Amanda E.

AU - Ambrosone, Christine B.

AU - Yannoukakos, Drakoulis

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - McLean, Catriona

AU - Fasching, Peter A.

AU - Haeberle, Lothar

AU - Ekici, Arif B

AU - Beckmann, Matthias W.

AU - Brenner, Hermann

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Swerdlow, Anthony J

AU - Ashworth, Alan

AU - Orr, Nick

AU - Jones, Michael

AU - Figueroa, Jonine D

AU - Garcia-Closas, Montserrat

AU - Brinton, Louise

AU - Lissowska, Jolanta

AU - Dumont, Martine

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon-Dschun

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Bonanni, Bernardo

AU - Radice, Paolo

AU - Bogdanova, Natalia

AU - Antonenkova, Natalia

AU - Dörk, Thilo

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M.

AU - Devilee, Peter

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J.

AU - Jakubowska, Anna

AU - Lubiski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Hamann, Ute

AU - Torres, Diana

AU - Schmutzler, Rita K.

AU - Neuhausen, Susan L

AU - Anton-Culver, Hoda

AU - Kristensen, Vessela N.

AU - Grenaker Alnæs, Grethe I.

AU - Pierce, Brandon L.

AU - Kraft, Peter

AU - Peters, Ulrike

AU - Lindstrom, Sara

AU - Seminara, Daniela

AU - Burgess, Stephen

AU - Ahsan, Habibul

AU - Whittemore, Alice S

AU - John, Esther M.

AU - Gammon, Marilie D.

AU - Malone, Kathleen E.

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Ahmed, Shahana

AU - Maranian, Mel J.

AU - Healey, Catherine S.

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Alonso, M. Rosario

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Pharoah, Paul D P

AU - Simard, Jacques

AU - Hall, Per

AU - Hunter, David J.

AU - Easton, Douglas F

AU - Zheng, Wei

AU - the DRIVE Project

AU - kConFab Investigators

AU - Australian Ovarian study group

AU - The GENICA Network

PY - 2015/11

Y1 - 2015/11

N2 - Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5 216 302 women, including 113 178 events. In a consortium with individual-level data from 46 325 case patients and 42 482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16 003 case patients and 41 335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10 cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10 cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5 × 10-8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.

AB - Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5 216 302 women, including 113 178 events. In a consortium with individual-level data from 46 325 case patients and 42 482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16 003 case patients and 41 335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10 cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10 cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5 × 10-8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84981313727&partnerID=8YFLogxK

U2 - 10.1093/jnci/djv219

DO - 10.1093/jnci/djv219

M3 - Article

AN - SCOPUS:84981313727

SN - 0027-8874

VL - 107

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 11

M1 - djv219

ER -

Height and breast cancer risk: Evidence from prospective studies and mendelian randomization

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