Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.
By: 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,
Department of Medicine, University of Chicago, Chicago, IL, USA.
2019-01-25; doi: 10.1038/s41416-019-0492-8
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.
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.
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).
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.
PMID:
31213659
