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- Title
Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.
- Authors
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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Publication
British Journal of Cancer, 2019, Vol 121, Issue 2, p180
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-019-0492-8