TY - JOUR
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
N1 - Funding Information:
Competing interests: G.P. received honoraria and grant from Pfizer, Roche, Novartis, Accord, AstraZeneca, Amgen, Accord and Lilly. R.S. served on advisory board for Tesaro, Clovis, Astra Zeneca, Ethicon and Genmab, and speaker’s bureau for Tesaro and Genentech. The other authors declare no competing interests.
Publisher Copyright:
© 2019, Cancer Research UK.
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
C2 - 31213659
AN - SCOPUS:85067846442
VL - 121
SP - 180
EP - 192
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 2
ER -