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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Authors
Qian, FrankRookus, 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
Caldés, Trinidad
Caligo, Maria A
Campbell, Ian
Carter, Jonathan
Chiquette, Jocelyne
Chung, Wendy K
Claes, Kathleen B M
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 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 E
Tung, Nadine
van Asperen, Christi J
van Engelen, Klaartje
van Rensburg, Elizabeth J
Venat-Bouvet, Laurence
Vierstraete, Jeroen
Wagner, Gabriel
Walker, Lisa
Weitzel, Jeffrey N
Yannoukakos, Drakoulis
Antoniou, Antonis C
Goldgar, David E
Olopade, Olufunmilayo I
Chenevix-Trench, Georgia
Rebbeck, Timothy R
Huo, Dezheng
Issue Date
2019-07
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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. 2019, 121(2):180-192 Br J CancerAbstract
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). 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.Description
To access publisher's full text version of this article click on the hyperlink belowAdditional Links
https://www.nature.com/articles/s41416-019-0492-8https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738050/
ae974a485f413a2113503eed53cd6c53
10.1038/s41416-019-0492-8
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