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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

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/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 (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.

Type Journal
ISBN 0007-0920
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, Mgem; 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.; Feliubadalo, L.; Foretova, L.; Friedman, E.; Frost, D.; Ganz, P. A.; Garber, J.; Garcia-Barberan, V.; Gehrig, A.; Glendon, G.; Godwin, A. K.; Gomez Garcia, E. B.; 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., et al.
Publisher Name British Journal of Cancer
Published Date 2019-06-20
Published Volume 121
Published Issue 2
Published Pages 180-192
Status Published in-print
DOI 10.1038/s41416-019-0492-8