Imperial College London
Alternate

DrKostasTsilidis

Faculty of Medicine, School of Public Health

Reader in Cancer Epidemiology and Prevention
 
 
 
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Contact

 

+44 (0)20 7594 2623k.tsilidis

 
 
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Location

 

School of Public HealthWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tang:2022:10.1186/s12916-022-02660-2,
author = {Tang, SN and Zuber, V and Tsilidis, K},
doi = {10.1186/s12916-022-02660-2},
journal = {BMC Medicine},
pages = {1--14},
title = {Identifying and ranking causal biochemical biomarkers for breast cancer: a Mendelian randomisation study},
url = {http://dx.doi.org/10.1186/s12916-022-02660-2},
volume = {20},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Only a few of the 34 biochemical biomarkers measured in the UK Biobank (UKB) have been associated with breast cancer, with many associations suffering from possible confounding and reverse causation. This study aimed to screen and rank all UKB biochemical biomarkers for possible causal relationships with breast cancer.Methods:We conducted two-sample Mendelian randomisation (MR) analyses on ~420,000 women by leveraging summary-level genetic exposure associations from the UKB study (n = 194,174) and summary-level genetic outcome associations from the Breast Cancer Association Consortium (n = 228,951). Our exposures included all 34 biochemical biomarkers in the UKB, and our outcomes were overall, oestrogen-positive, and oestrogen-negative breast cancer. We performed inverse-variance weighted MR, weighted median MR, MR-Egger, and MR-PRESSO for 30 biomarkers for which we found multiple instrumental variables. We additionally performed multivariable MR to adjust for known risk factors, bidirectional MR to investigate reverse causation, and MR Bayesian model averaging to rank the significant biomarkers by their genetic evidence.Results:Increased genetic liability to overall breast cancer was robustly associated with the following biomarkers by decreasing importance: testosterone (odds ratio (OR): 1.12, 95% confidence interval (CI): 1.04–1.21), high-density lipoprotein (HDL) cholesterol (OR: 1.08, 95% CI: 1.04–1.13), insulin-like growth factor 1 (OR: 1.08, 95% CI: 1.02–1.13), and alkaline phosphatase (ALP) (OR: 0.93, 95% CI: 0.89–0.98).ConclusionsOur findings support a likely causal role of genetically predicted levels of testosterone, HDL cholesterol, and IGF-1, as well as a novel potential role of ALP in breast cancer aetiology. Further studies are needed to understand full disease pathways that may inform breast cancer prevention.
AU  - Tang,SN
AU  - Zuber,V
AU  - Tsilidis,K
DO  - 10.1186/s12916-022-02660-2
EP  - 14
PY  - 2022///
SN  - 1741-7015
SP  - 1
TI  - Identifying and ranking causal biochemical biomarkers for breast cancer: a Mendelian randomisation study
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-022-02660-2
UR  - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02660-2
UR  - http://hdl.handle.net/10044/1/101644
VL  - 20
ER  -
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