학술논문
Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers
Document Type
article
Author
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 GEM; Azzollini, Jacopo; Barrowdale, Daniel; Barwell, Julian; Benitez, Javier; Białkowska, Katarzyna; Bonadona, Valérie; Borde, Julika; Borg, Ake; Bradbury, Angela R; Brunet, Joan; Buys, Saundra S; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Carter, Jonathan; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen BM; Collée, J Margriet; Collonge-Rame, Marie-Agnès; Couch, Fergus J; Daly, Mary B; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dorfling, Cecilia M; Eason, Jacqueline; Easton, Douglas F; Eeles, Ros; Engel, Christoph; Evans, D Gareth; Faivre, Laurence; Feliubadaló, Lidia; Foretova, Lenka; Friedman, Eitan; Frost, Debra; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gehrig, Andrea; Glendon, Gord; Godwin, Andrew K; Gómez 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; Lázaro, Conxi; Leroux, Dominique; Lester, Jenny; Lesueur, Fabienne; Loud, Jennifer T; Lubiński, Jan; Łukomska, Alicja; McGuffog, Lesley; Mebirouk, Noura; Meijers-Heijboer, Hanne EJ; 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
Source
British Journal of Cancer. 121(2)
Subject
Language
Abstract
BackgroundHeight 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.MethodsWe 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.ResultsObserved 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