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Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.

Accepted version
Peer-reviewed

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Authors

Lee, Wei-Hsuan 
Kar, Siddhartha 

Abstract

BACKGROUND: Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation. METHODS: Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10-8) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis. RESULTS: A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer. CONCLUSIONS: These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.

Description

Keywords

Biological Specimen Banks, Genome-Wide Association Study, Humans, Hydrocortisone, Mendelian Randomization Analysis, Neoplasms, Polymorphism, Single Nucleotide, United Kingdom

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

125

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MC_UU_00002/7)
National Institute for Health and Care Research (IS-BRC-1215-20014)