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Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Neumeyer, Sonja 
Banbury, Barbara L 
Arndt, Volker 
Berndt, Sonja I 
Bezieau, Stephane 

Abstract

BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

Description

Keywords

Age Factors, Case-Control Studies, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Menarche, Mendelian Randomization Analysis, Menopause, Polymorphism, Single Nucleotide, Registries

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

118

Publisher

Springer Science and Business Media LLC