Body mass index and breast cancer survival: a Mendelian randomization analysis

Qi Guo; Stephen Burgess; Constance Turman; Manjeet K Bolla; Qin Wang; Michael Lush; Jean Abraham; Kristiina Aittomäki; Irene L Andrulis; Carmel Apicella; Volker Arndt; Myrto Barrdahl; Javier Benitez; Christine D Berg; Carl Blomqvist; Stig E Bojesen; Bernardo Bonanni; Judith S Brand; Hermann Brenner; Annegien Broeks; Barbara Burwinkel; Carlos Caldas; Daniele Campa; Federico Canzian; Jenny Chang-Claude; Stephen J Chanock; Suet-Feung Chin; Fergus J Couch; Angela Cox; Simon S Cross; Cezary Cybulski; Kamila Czene; Hatef Darabi; Peter Devilee; W Ryan Diver; Alison M Dunning; Helena M Earl; Diana M Eccles; Arif B Ekici; Mikael Eriksson; D Gareth Evans; Peter A Fasching; Jonine Figueroa; Dieter Flesch-Janys; Henrik Flyger; Susan M Gapstur; Mia M Gaudet; Graham G Giles; David J Hunter; Jose I A Perez; kConFab/AOCS Investigators

doi:10.1093/ije/dyx131

Body mass index and breast cancer survival: a Mendelian randomization analysis

Qi Guo
, Stephen Burgess
, Constance Turman
, Manjeet K Bolla
, Qin Wang
, Michael Lush
, Jean Abraham
, Kristiina Aittomäki
, Irene L Andrulis
, Carmel Apicella
, Volker Arndt
, Myrto Barrdahl
, Javier Benitez
, Christine D Berg
, Carl Blomqvist
, Stig E Bojesen
, Bernardo Bonanni
, Judith S Brand
, Hermann Brenner
, Annegien Broeks

Barbara Burwinkel, Carlos Caldas, Daniele Campa, Federico Canzian, Jenny Chang-Claude, Stephen J Chanock, Suet-Feung Chin, Fergus J Couch, Angela Cox, Simon S Cross, Cezary Cybulski, Kamila Czene, Hatef Darabi, Peter Devilee, W Ryan Diver, Alison M Dunning, Helena M Earl, Diana M Eccles, Arif B Ekici, Mikael Eriksson, D Gareth Evans, Peter A Fasching, Jonine Figueroa, Dieter Flesch-Janys, Henrik Flyger, Susan M Gapstur, Mia M Gaudet, Graham G Giles, David J Hunter, Jose I A Perez, kConFab/AOCS Investigators

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Abstract

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.

Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.

Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).

Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

Original language	English
Pages (from-to)	1814-1822
Number of pages	9
Journal	International Journal of Epidemiology
Volume	46
Issue number	6
Early online date	9 Oct 2017
DOIs	https://doi.org/10.1093/ije/dyx131
Publication status	Published - 1 Dec 2017

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

SDG 3 Good Health and Well-being

Keywords

Body mass index
breast cancer survival
Mendelian randomization
epidemiology
genetics

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Guo, Q., Burgess, S., Turman, C., Bolla, M. K., Wang, Q., Lush, M., Abraham, J., Aittomäki, K., Andrulis, I. L., Apicella, C., Arndt, V., Barrdahl, M., Benitez, J., Berg, C. D., Blomqvist, C., Bojesen, S. E., Bonanni, B., Brand, J. S., Brenner, H., ... kConFab/AOCS Investigators (2017). Body mass index and breast cancer survival: a Mendelian randomization analysis. International Journal of Epidemiology, 46(6), 1814-1822. https://doi.org/10.1093/ije/dyx131

@article{e9fa7c04d2ad45d18d6fcfc0ed65d880,

title = "Body mass index and breast cancer survival: a Mendelian randomization analysis",

abstract = "Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95\% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95\% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.",

keywords = "Body mass index, breast cancer survival, Mendelian randomization, epidemiology, genetics",

author = "Qi Guo and Stephen Burgess and Constance Turman and Bolla, \{Manjeet K\} and Qin Wang and Michael Lush and Jean Abraham and Kristiina Aittom{\"a}ki and Andrulis, \{Irene L\} and Carmel Apicella and Volker Arndt and Myrto Barrdahl and Javier Benitez and Berg, \{Christine D\} and Carl Blomqvist and Bojesen, \{Stig E\} and Bernardo Bonanni and Brand, \{Judith S\} and Hermann Brenner and Annegien Broeks and Barbara Burwinkel and Carlos Caldas and Daniele Campa and Federico Canzian and Jenny Chang-Claude and Chanock, \{Stephen J\} and Suet-Feung Chin and Couch, \{Fergus J\} and Angela Cox and Cross, \{Simon S\} and Cezary Cybulski and Kamila Czene and Hatef Darabi and Peter Devilee and Diver, \{W Ryan\} and Dunning, \{Alison M\} and Earl, \{Helena M\} and Eccles, \{Diana M\} and Ekici, \{Arif B\} and Mikael Eriksson and Evans, \{D Gareth\} and Fasching, \{Peter A\} and Jonine Figueroa and Dieter Flesch-Janys and Henrik Flyger and Gapstur, \{Susan M\} and Gaudet, \{Mia M\} and Giles, \{Graham G\} and Hunter, \{David J\} and Perez, \{Jose I A\} and \{kConFab/AOCS Investigators\}",

year = "2017",

month = dec,

day = "1",

doi = "10.1093/ije/dyx131",

language = "English",

volume = "46",

pages = "1814--1822",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "6",

}

Guo, Q, Burgess, S, Turman, C, Bolla, MK, Wang, Q, Lush, M, Abraham, J, Aittomäki, K, Andrulis, IL, Apicella, C, Arndt, V, Barrdahl, M, Benitez, J, Berg, CD, Blomqvist, C, Bojesen, SE, Bonanni, B, Brand, JS, Brenner, H, Broeks, A, Burwinkel, B, Caldas, C, Campa, D, Canzian, F, Chang-Claude, J, Chanock, SJ, Chin, S-F, Couch, FJ, Cox, A, Cross, SS, Cybulski, C, Czene, K, Darabi, H, Devilee, P, Diver, WR, Dunning, AM, Earl, HM, Eccles, DM, Ekici, AB, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flesch-Janys, D, Flyger, H, Gapstur, SM, Gaudet, MM, Giles, GG, Hunter, DJ, Perez, JIA & kConFab/AOCS Investigators 2017, 'Body mass index and breast cancer survival: a Mendelian randomization analysis', International Journal of Epidemiology, vol. 46, no. 6, pp. 1814-1822. https://doi.org/10.1093/ije/dyx131

TY - JOUR

T1 - Body mass index and breast cancer survival

T2 - a Mendelian randomization analysis

AU - Guo, Qi

AU - Burgess, Stephen

AU - Turman, Constance

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Lush, Michael

AU - Abraham, Jean

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L

AU - Apicella, Carmel

AU - Arndt, Volker

AU - Barrdahl, Myrto

AU - Benitez, Javier

AU - Berg, Christine D

AU - Blomqvist, Carl

AU - Bojesen, Stig E

AU - Bonanni, Bernardo

AU - Brand, Judith S

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Burwinkel, Barbara

AU - Caldas, Carlos

AU - Campa, Daniele

AU - Canzian, Federico

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J

AU - Chin, Suet-Feung

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Cybulski, Cezary

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Devilee, Peter

AU - Diver, W Ryan

AU - Dunning, Alison M

AU - Earl, Helena M

AU - Eccles, Diana M

AU - Ekici, Arif B

AU - Eriksson, Mikael

AU - Evans, D Gareth

AU - Fasching, Peter A

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Flyger, Henrik

AU - Gapstur, Susan M

AU - Gaudet, Mia M

AU - Giles, Graham G

AU - Hunter, David J

AU - Perez, Jose I A

AU - kConFab/AOCS Investigators

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

AB - Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

KW - Body mass index

KW - breast cancer survival

KW - Mendelian randomization

KW - epidemiology

KW - genetics

U2 - 10.1093/ije/dyx131

DO - 10.1093/ije/dyx131

M3 - Article (Academic Journal)

C2 - 29232439

SN - 0300-5771

VL - 46

SP - 1814

EP - 1822

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 6

ER -

Body mass index and breast cancer survival: a Mendelian randomization analysis

Abstract

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Keywords

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