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 \textless 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.

DOI: 10.1038/s41416-019-0492-8

Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Publication type: Journal article

Journal: British journal of cancer

Human Diseases: Hereditary breast ovarian cancer syndrome

Citation: Br J Cancer 121(2):180-192

Date Published: 1st Jul 2019

Registered Mode: imported from a bibtex file

Authors: Frank Qian, Matti A. Rookus, Goska Leslie, Harvey A. Risch, Mark H. Greene, Cora M. Aalfs, Muriel A. Adank, Julian Adlard, Bjarni A. Agnarsson, Munaza Ahmed, Kristiina Aittomäki, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Margreet G. E. M. Ausems, Jacopo Azzollini, Daniel Barrowdale, Julian Barwell, Javier Benitez, Katarzyna Białkowska, Valérie Bonadona, Julika Borde, Ake Borg, Angela R. Bradbury, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Jonathan Carter, Jocelyne Chiquette, Wendy K. Chung, Kathleen B. M. Claes, J. Margriet Collée, Marie-Agnès Collonge-Rame, Fergus J. Couch, Mary B. Daly, Capucine Delnatte, Orland Diez, Susan M. Domchek, Cecilia M. Dorfling, Jacqueline Eason, Douglas F. Easton, Ros Eeles, Christoph Engel, D. Gareth Evans, Laurence Faivre, Lidia Feliubadaló, Lenka Foretova, Eitan Friedman, Debra Frost, Patricia A. Ganz, Judy Garber, Vanesa Garcia-Barberan, Andrea Gehrig, Gord Glendon, Andrew K. Godwin, Encarna B. Gómez Garcia, Ute Hamann, Jan Hauke, John L. Hopper, Peter J. Hulick, Evgeny N. Imyanitov, Claudine Isaacs, Louise Izatt, Anna Jakubowska, Ramunas Janavicius, Esther M. John, Beth Y. Karlan, Carolien M. Kets, Yael Laitman, Conxi Lázaro, Dominique Leroux, Jenny Lester, Fabienne Lesueur, Jennifer T. Loud, Jan Lubiński, Alicja Łukomska, Lesley McGuffog, Noura Mebirouk, Hanne E. J. Meijers-Heijboer, Alfons Meindl, Austin Miller, Marco Montagna, Thea M. Mooij, Emmanuelle Mouret-Fourme, Katherine L. Nathanson, Bita Nehoray, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Kenneth Offit, Edith Olah, Kai-Ren Ong, Jan C. Oosterwijk, Laura Ottini, Michael T. Parsons, Paolo Peterlongo, Georg Pfeiler, Nisha Pradhan, Paolo Radice, Susan J. Ramus, Johanna Rantala, Gad Rennert, Mark Robson, Gustavo C. Rodriguez, Ritu Salani, Maren T. Scheuner, Rita K. Schmutzler, Payal D. Shah, Lucy E. Side, Jacques Simard, Christian F. Singer, Doris Steinemann, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R. Teixeira, Mary Beth Terry, Mads Thomassen, Marc Tischkowitz, Silvia Tognazzo, Amanda E. Toland, Nadine Tung, Christi J. van Asperen, Klaartje van Engelen, Elizabeth J. van Rensburg, Laurence Venat-Bouvet, Jeroen Vierstraete, Gabriel Wagner, Lisa Walker, Jeffrey N. Weitzel, Drakoulis Yannoukakos, Antonis C. Antoniou, David E. Goldgar, Olufunmilayo I. Olopade, Georgia Chenevix-Trench, Timothy R. Rebbeck, Dezheng Huo

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René Hänsel

Citation

Qian, F., , Rookus, M. A., Leslie, G., Risch, H. A., Greene, M. H., Aalfs, C. M., Adank, M. A., Adlard, J., Agnarsson, B. A., Ahmed, M., Aittomäki, K., Andrulis, I. L., Arnold, N., Arun, B. K., Ausems, M. G. E. M., Azzollini, J., Barrowdale, D., Barwell, J., … . (2019). 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 (Vol. 121, Issue 2, pp. 180–192). Springer Science and Business Media LLC. https://doi.org/10.1038/s41416-019-0492-8

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Created: 15th Jul 2020 at 12:51

Last updated: 7th Dec 2021 at 17:58

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

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