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; Sune F Nielsen; Børge G Nordestgaard; 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 BroeksBarbara 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, Sune F Nielsen, Børge G Nordestgaard, kConFab/AOCS Investigators

45 Citations (Scopus)

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
Journal	International Journal of Epidemiology
Volume	46
Issue number	6
Pages (from-to)	1814-1822
Number of pages	9
ISSN	0300-5771
DOIs	https://doi.org/10.1093/ije/dyx131
Publication status	Published - 1 Dec 2017

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10.1093/ije/dyx131

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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

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, Nielsen, SF , Nordestgaard, BG & 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

@article{a1d97141bcf24b7ab33dbc553a6781f2,

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 = "Journal Article",

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 Nielsen, \{Sune F\} and Nordestgaard, \{B{\o}rge G\} 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",

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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 - Nielsen, Sune F

AU - Nordestgaard, Børge G

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 - Journal Article

UR - https://www.scopus.com/pages/publications/85039549212

U2 - 10.1093/ije/dyx131

DO - 10.1093/ije/dyx131

M3 - Journal article

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

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