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Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Dixon-Suen, Suzanne C  ORCID logo  https://orcid.org/0000-0003-3714-8386
Nagle, Christina M 
Thrift, Aaron P 
Pharoah, Paul DP 
Ewing, Ailith 

Abstract

BACKGROUND: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. METHODS: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. RESULTS: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. CONCLUSIONS: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

Description

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Body Height, Carcinoma, Ovarian Epithelial, Case-Control Studies, Female, Genetic Predisposition to Disease, Geography, Humans, Mendelian Randomization Analysis, Middle Aged, Ovarian Neoplasms, Risk Factors, Young Adult

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

118

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)
National Institutes of Health (NIH) (via H Lee Moffitt Cancer Center & Research Institute) (SUBAWARD # 10-15915-01-03-G2)
Cancer Research Uk (None)
National Cancer Institute (U19CA148065)
National Cancer Institute (U19CA148537)
Cancer Research UK (12014)
Cancer Research UK (10118)
National Cancer Institute (R01CA128978)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (16565)