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Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: A Mendelian randomisation analysis

Culliford, Richard, Cornish, Alex J., Law, Philip J., Farrington, Susan M., Palin, Kimmo, Jenkins, Mark A., Casey, Graham, Hoffmeister, Michael, Brenner, Hermann, Chang-Claude, Jenny, Kirac, Iva, Maughan, Tim, Brezina, Stefanie, Gsur, Andrea, Cheadle, Jeremy P., Aaltonen, Lauri A., Dunlop, Malcom G. and Soulston, Richard S. 2021. Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: A Mendelian randomisation analysis. British Journal of Cancer 10.1038/s41416-020-01211-x

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Abstract

Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Publisher: Springer Nature
ISSN: 0007-0920
Related URLs:
Date of First Compliant Deposit: 8 January 2021
Date of Acceptance: 25 November 2020
Last Modified: 12 Jan 2021 17:02
URI: http://orca.cf.ac.uk/id/eprint/137507

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