Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

KConFab investigators, HEBON Investigators, GEMO Study Collaborators, EMBRACE Collaborators

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

Original languageEnglish (US)
Pages (from-to)180-192
Number of pages13
JournalBritish journal of cancer
Volume121
Issue number2
DOIs
StatePublished - Jul 16 2019

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Random Allocation
Ovarian Neoplasms
Body Mass Index
Mutation
Confidence Intervals
Proportional Hazards Models
Population
Odds Ratio
Research Personnel
Observation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. / KConFab investigators; HEBON Investigators; GEMO Study Collaborators; EMBRACE Collaborators.

In: British journal of cancer, Vol. 121, No. 2, 16.07.2019, p. 180-192.

Research output: Contribution to journalArticle

KConFab investigators ; HEBON Investigators ; GEMO Study Collaborators ; EMBRACE Collaborators. / Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. In: British journal of cancer. 2019 ; Vol. 121, No. 2. pp. 180-192.
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title = "Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers",
abstract = "Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95{\%} confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95{\%} CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95{\%} CI: 1.06–1.48) and HR = 1.59 (95{\%} CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.",
author = "{KConFab investigators} and {HEBON Investigators} and {GEMO Study Collaborators} and {EMBRACE Collaborators} and Frank Qian and Rookus, {Matti A.} and Goska Leslie and Risch, {Harvey A.} and Greene, {Mark H.} and Aalfs, {Cora M.} and Adank, {Muriel A.} and Julian Adlard and Agnarsson, {Bjarni A.} and Munaza Ahmed and Kristiina Aittom{\"a}ki and Andrulis, {Irene L.} and Norbert Arnold and Arun, {Banu K.} and Ausems, {Margreet G.E.M.} and Jacopo Azzollini and Daniel Barrowdale and Julian Barwell and Javier Benitez and Katarzyna Białkowska and Val{\'e}rie Bonadona and Julika Borde and Ake Borg and Bradbury, {Angela R.} and Joan Brunet and Buys, {Saundra S.} and Trinidad Cald{\'e}s and Caligo, {Maria A.} and Ian Campbell and Jonathan Carter and Jocelyne Chiquette and Chung, {Wendy K.} and Claes, {Kathleen B.M.} and Coll{\'e}e, {J. Margriet} and Collonge-Rame, {Marie Agn{\`e}s} and Couch, {Fergus J.} and Daly, {Mary B.} and Capucine Delnatte and Orland Diez and Domchek, {Susan M.} and Dorfling, {Cecilia M.} and Jacqueline Eason and Easton, {Douglas F.} and Ros Eeles and Christoph Engel and Evans, {D. Gareth} and Laurence Faivre and Lidia Feliubadal{\'o} and Lenka Foretova and Eitan Friedman",
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T1 - Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

AU - KConFab investigators

AU - HEBON Investigators

AU - GEMO Study Collaborators

AU - EMBRACE Collaborators

AU - Qian, Frank

AU - Rookus, Matti A.

AU - Leslie, Goska

AU - Risch, Harvey A.

AU - Greene, Mark H.

AU - Aalfs, Cora M.

AU - Adank, Muriel A.

AU - Adlard, Julian

AU - Agnarsson, Bjarni A.

AU - Ahmed, Munaza

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Arnold, Norbert

AU - Arun, Banu K.

AU - Ausems, Margreet G.E.M.

AU - Azzollini, Jacopo

AU - Barrowdale, Daniel

AU - Barwell, Julian

AU - Benitez, Javier

AU - Białkowska, Katarzyna

AU - Bonadona, Valérie

AU - Borde, Julika

AU - Borg, Ake

AU - Bradbury, Angela R.

AU - Brunet, Joan

AU - Buys, Saundra S.

AU - Caldés, Trinidad

AU - Caligo, Maria A.

AU - Campbell, Ian

AU - Carter, Jonathan

AU - Chiquette, Jocelyne

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Collée, J. Margriet

AU - Collonge-Rame, Marie Agnès

AU - Couch, Fergus J.

AU - Daly, Mary B.

AU - Delnatte, Capucine

AU - Diez, Orland

AU - Domchek, Susan M.

AU - Dorfling, Cecilia M.

AU - Eason, Jacqueline

AU - Easton, Douglas F.

AU - Eeles, Ros

AU - Engel, Christoph

AU - Evans, D. Gareth

AU - Faivre, Laurence

AU - Feliubadaló, Lidia

AU - Foretova, Lenka

AU - Friedman, Eitan

PY - 2019/7/16

Y1 - 2019/7/16

N2 - Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

AB - Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

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U2 - 10.1038/s41416-019-0492-8

DO - 10.1038/s41416-019-0492-8

M3 - Article

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VL - 121

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EP - 192

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

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