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{Bueno-de-Mesquita:2020:10.1186/s12916-020-01703-w,
author = {Bueno-de-Mesquita, B and Cross, A and Aune, D and Tsilidis, K},
doi = {10.1186/s12916-020-01703-w},
journal = {BMC Medicine},
pages = {1--15},
title = {Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses},
url = {http://dx.doi.org/10.1186/s12916-020-01703-w},
volume = {18},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported antioxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5x10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity=0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin, were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P=0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P=0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were
AU  - Bueno-de-Mesquita,B
AU  - Cross,A
AU  - Aune,D
AU  - Tsilidis,K
DO  - 10.1186/s12916-020-01703-w
EP  - 15
PY  - 2020///
SN  - 1741-7015
SP  - 1
TI  - Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-020-01703-w
UR  - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01703-w
UR  - http://hdl.handle.net/10044/1/81414
VL  - 18
ER  -
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