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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Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers
Qian, Frank; Rookus, Matti A.; Leslie, Goska; Risch, Harvey A.; Greene, Mark H.; Aalfs, Cora M.; Adank, Muriel A.; Adlard, Julian; Agnarsson, Bjarni A.; Ahmed, Munaza; Aittomäki, Kristiina; Andrulis, Irene L.; Arnold, Norbert; Arun, Banu K.; Ausems, Margreet G.E.M.; Azzollini, Jacopo; Barrowdale, Daniel; Barwell, Julian; Benitez, Javier; Białkowska, Katarzyna; Bonadona, Valérie; Borde, Julika; Borg, Ake; Bradbury, Angela R.; Brunet, Joan; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Carter, Jonathan; Chiquette, Jocelyne; Chung, Wendy K.; Claes, Kathleen B.M.; Collee, J. Margriet; Collonge-Rame, Marie-Agnes; Couch, Fergus J.; Daly, Mary B.; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dorfling, Cecilia Maria; Eason, Jacqueline; Easton, Douglas F.; Eeles, Ros; Engel, Christoph; Evans, D. Gareth; Faivre, Laurence; Feliubadalo, Lidia; Foretova, Lenka; Friedman, Eitan; Frost, Debra; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gehrig, Andrea; Glendon, Gord; Godwin, Andrew K.; Gomez Garcia, Encarna B.; Hamann, Ute; Hauke, Jan; Hopper, John L.; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; Janavicius, Ramunas; John, Esther M.; Karlan, Beth Y.; Kets, Carolien M.; Laitman, Yael; Lazaro, Conxi; Leroux, Dominique; Lester, Jenny; Lesueur, Fabienne; Loud, Jennifer T.; Lubinski, Jan; Lukomska, Alicja; McGuffog, Lesley; Mebirouk, Noura; Meijers-Heijboer, Hanne E.J.; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mooij, Thea M.; Mouret-Fourme, Emmanuelle; Nathanson, Katherine L.; Nehoray, Bita; Neuhausen, Susan L.; Nevanlinna, Heli; Nielsen, Finn C.; Offit, Kenneth; Olah, Edith; Ong, Kai-ren; Oosterwijk, Jan C.; Ottini, Laura; Parsons, Michael T.; Peterlongo, Paolo; Pfeiler, Georg; Pradhan, Nisha; Radice, Paolo; Ramus, Susan J.; Rantala, Johanna; Rennert, Gad; Robson, Mark; Rodriguez, Gustavo C.; Salani, Ritu; Scheuner, Maren T.; Schmutzler, Rita K.; Shah, Payal D.; Side, Lucy E.; Simard, Jacques; Singer, Christian F.; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Tan, Yen Yen; Teixeira, Manuel R.; Terry, Mary Beth; Thomassen, Mads; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; Van Asperen, Christi J.; Van Engelen, Klaartje; Jansen van Rensburg, Elizabeth; Venat-Bouvet, Laurence; Vierstraete, Jeroen; Wagner, Gabriel; Walker, Lisa; Weitzel, Jeffrey N.; Yannoukakos, Drakoulis; KConFab Investigators; HEBON Investigators; GEMO Study Collaborators; EMBRACE Collaborators; Antoniou, Antonis C.; Goldgar, David E.; Olopade, Olufunmilayo I.; Chenevix-Trench, Georgia; Rebbeck, Timothy R.; Huo, Dezheng
Date:
2019-07
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).
CONCUSION : 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.
