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Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Endometrial Cancer | Research article

Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk

Authors: Shannon D’Urso, Pooja Arumugam, Therese Weider, Liang-Dar Hwang, Tom A. Bond, John P. Kemp, Nicole M. Warrington, David M. Evans, Tracy A. O’Mara, Gunn-Helen Moen

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk. 

Methods

We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman’s number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

Results

We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p = 0.036) independent of BMI, age at menarche and age at menopause.

Conclusions

MVMR analysis showed that the number of live births causally reduced the risk of EC.
Appendix
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Metadata
Title
Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk
Authors
Shannon D’Urso
Pooja Arumugam
Therese Weider
Liang-Dar Hwang
Tom A. Bond
John P. Kemp
Nicole M. Warrington
David M. Evans
Tracy A. O’Mara
Gunn-Helen Moen
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02585-w

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