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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.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Qian, Frank 
Rookus, Matti A 
Leslie, Goska 
Risch, Harvey A 
Greene, Mark H 

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/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

Keywords

Adult, Aged, Body Height, Body Mass Index, Female, Genes, BRCA1, Genes, BRCA2, Heterozygote, Humans, Mendelian Randomization Analysis, Menopause, Middle Aged, Mutation, Ovarian Neoplasms, Proportional Hazards Models

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

121

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (20861)
Medical Research Council (MR/P012930/1)
National Cancer Institute (U19CA148537)
National Cancer Institute (U19CA148065)
Cancer Research UK (12014)
National Cancer Institute (R01CA128978)
European Commission (223175)
Cancer Research UK (10118)
European Research Council (310018)
Cancer Research UK (11990)
Cancer Research UK (23382)
Cancer Research UK (16565)