Imperial College London
Dr Neil Murphy

DrNeilMurphy

Faculty of Medicine, School of Public Health

Honorary Senior Research Fellow
 
 
 
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Contact

 

neil.murphy

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bull:2023:10.1101/2023.03.10.23287084,
author = {Bull, CJ and Hazelwood, E and Bell, JA and Tan, VY and Constantinescu, A-E and Borges, MC and Legge, DN and Burrows, K and Huyghe, JR and Brenner, H and Castellví-Bel, S and Chan, AT and Kweon, S-S and Marchand, LL and Li, L and Cheng, I and Pai, RK and Figueiredo, JC and Murphy, N and Gunter, MJ and Timpson, NJ and Vincent, EE},
doi = {10.1101/2023.03.10.23287084},
journal = {medRxiv},
title = {Identifying metabolic features of colorectal cancer liability using Mendelian randomization.},
url = {http://dx.doi.org/10.1101/2023.03.10.23287084},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. METHODS: To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. RESULTS: The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. CONCLUSIONS: These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development. FUNDING: This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used
AU  - Bull,CJ
AU  - Hazelwood,E
AU  - Bell,JA
AU  - Tan,VY
AU  - Constantinescu,A-E
AU  - Borges,MC
AU  - Legge,DN
AU  - Burrows,K
AU  - Huyghe,JR
AU  - Brenner,H
AU  - Castellví-Bel,S
AU  - Chan,AT
AU  - Kweon,S-S
AU  - Marchand,LL
AU  - Li,L
AU  - Cheng,I
AU  - Pai,RK
AU  - Figueiredo,JC
AU  - Murphy,N
AU  - Gunter,MJ
AU  - Timpson,NJ
AU  - Vincent,EE
DO  - 10.1101/2023.03.10.23287084
PY  - 2023///
TI  - Identifying metabolic features of colorectal cancer liability using Mendelian randomization.
T2  - medRxiv
UR  - http://dx.doi.org/10.1101/2023.03.10.23287084
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36945480
ER  -
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