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

Qian, F.; Rookus, M.A.; Leslie, G.; Risch, H.A.; Greene, M.H.; Aalfs, C.M.; ... ; CIMBA (2019)

Article / Letter to editor

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/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P-interaction < 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.

• All authors: 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.; Aittomaki, K.; Andrulis, I.L.; Arnold, N.; Arun, B.K.; Ausems, M.G.E.M.; Azzollini, J.; Barrowdale, D.; Barwell, J.; Benitez, J.; Bialkowska, K.; Bonadona, V.; Borde, J.; Borg, A.; Bradbury, A.R.; Brunet, J.; Buys, S.S.; Caldes, T.; Caligo, M.A.; Campbell, I.; Carter, J.; Chiquette, J.; Chung, W.K.; Claes, K.B.M.; Collee, J.M.; Collonge-Rame, M.A.; Couch, F.J.; Daly, M.B.; Delnatte, C.; Diez, O.; Domchek, S.M.; Dorfling, C.M.; Eason, J.; Easton, D.F.; Eeles, R.; Engel, C.; Evans, D.G.; Faivre, L.; Feliubado, L.; Foretova, L.; Friedman, E.; Frost, D.; Ganz, P.A.; Garber, J.; Garcia-Barberan, V.; Gehrig, A.; Glendon, G.; Godwin, A.K.; Garcia, E.B.G.; Hamann, U.; Hauke, J.; Hopper, J.L.; Hulick, P.J.; Imyanitov, E.N.; Isaacs, C.; Izatt, L.; Jakubowska, A.; Janavicius, R.; John, E.M.; Karlan, B.Y.; Kets, C.M.; Laitman, Y.; Lazaro, C.; Leroux, D.; Lester, J.; Lesueur, F.; Loud, J.T.; Lubinski, J.; Lukomska, A.; McGuffog, L.; Mebirouk, N.; Meijers-Heijboer, H.E.J.; Meindl, A.; Miller, A.; Montagna, M.; Mooij, T.M.; Mouret-Fourme, E.; Nathanson, K.L.; Nehoray, B.; Neuhausen, S.L.; Nevanlinna, H.; Nielsen, F.C.; Offit, K.; Olah, E.; Ong, K.R.; Oosterwijk, J.C.; Ottini, L.; Parsons, M.T.; Peterlongo, P.; Pfeiler, G.; Pradhan, N.; Radice, P.; Ramus, S.J.; Rantala, J.; Rennert, G.; Robson, M.; Rodriguez, G.C.; Salani, R.; Scheuner, M.T.; Schmutzler, R.K.; Shah, P.D.; Side, L.E.; Simard, J.; Singer, C.F.; Steinemann, D.; Stoppa-Lyonnet, D.; Tan, Y.Y.; Teixeira, M.R.; Terry, M.B.; Thomassen, M.; Tischkowitz, M.; Tognazzo, S.; Toland, A.E.; Tung, N.; Asperen, C.J. van; Engelen, K. van; Rensburg, E.J. van; Venat-Bouvet, L.; Vierstraete, J.; Wagner, G.; Walker, L.; Weitze, J.N.; Yannoukakos, D.; Antoniou, A.C.; Goldgar, D.E.; Olopade, O.I.; Chenevix-Trench, G.; Rebbeck, T.R.; Huo, D.; KConFab Investigators; HEBON Investigators; GEMO Study Collaborators; EMBRACE Collaborators; CIMBA
• Date: 2019-07-16
• Journal: British Journal of Cancer
• Volume: 121
• Issue: 2
• Pages: 180 - 192
• DOI: doi:10.1038/s41416-019-0492-8