Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

Ben 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 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 Brand; Pascal Guénel; Thérèse Truong; kConFab Investigators, Australian Ovarian Study Group

doi:10.1093/jnci/djv219

Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

Ben 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 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 Brand, Pascal Guénel, Thérèse Truong, kConFab Investigators, Australian Ovarian Study Group

70 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	djv219
Tidsskrift	National Cancer Institute. Journal (Print)
Vol/bind	107
Udgave nummer	11
Sider (fra-til)	1-17
Antal sider	17
ISSN	0027-8874
DOI	https://doi.org/10.1093/jnci/djv219
Status	Udgivet - nov. 2015

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10.1093/jnci/djv219

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Zhang, B., 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., ... kConFab Investigators, Australian Ovarian Study Group (2015). Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization. National Cancer Institute. Journal (Print), 107(11), 1-17. Artikel djv219. https://doi.org/10.1093/jnci/djv219

Zhang, B, 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, C, 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, J, Guénel, P, Truong, T & kConFab Investigators, Australian Ovarian Study Group 2015, 'Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization', National Cancer Institute. Journal (Print), bind 107, nr. 11, djv219, s. 1-17. https://doi.org/10.1093/jnci/djv219

@article{ab2d6fb843e74290887ac0a62f931ad9,

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.",

keywords = "Body Height, Breast Neoplasms, Evidence-Based Medicine, Female, Humans, Mendelian Randomization Analysis, Odds Ratio, Prospective Studies, Risk Factors",

author = "Ben Zhang 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 Celine Vachon 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 Judith Brand and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and {kConFab Investigators, Australian Ovarian Study Group}",

year = "2015",

month = nov,

doi = "10.1093/jnci/djv219",

language = "English",

volume = "107",

pages = "1--17",

journal = "National Cancer Institute. Journal (Print)",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "11",

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TY - JOUR

T1 - Height and Breast Cancer Risk

T2 - Evidence From Prospective Studies and Mendelian Randomization

AU - Zhang, Ben

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

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

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - kConFab Investigators, Australian Ovarian Study Group

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.

KW - Body Height

KW - Breast Neoplasms

KW - Evidence-Based Medicine

KW - Female

KW - Humans

KW - Mendelian Randomization Analysis

KW - Odds Ratio

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1093/jnci/djv219

DO - 10.1093/jnci/djv219

M3 - Journal article

C2 - 26296642

SN - 0027-8874

VL - 107

SP - 1

EP - 17

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

IS - 11

M1 - djv219

ER -

Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

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