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

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ICR Authors

Culliford, Richard
 Cornish, Alexander
 Law, Philip
 Houlston, Richard

Authors

Culliford, R
Cornish, AJ
Law, PJ
Farrington, SM
Palin, K
Jenkins, MA
Casey, G
Hoffmeister, M
Brenner, H
Chang-Claude, J
Kirac, I
Maughan, T
Brezina, S
Gsur, A
Cheadle, JP
Aaltonen, LA
Dunlop, MG
Houlston, RS

Document Type

Journal Article

Date

2021-03-16

Date Accepted

2020-11-25

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.

Citation

British Journal of Cancer, 2021, 124 (6), pp. 1169 - 1174

DOI

10.1038/s41416-020-01211-x

URI

https://repository.icr.ac.uk/handle/internal/5585

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

British Journal of Cancer

Publisher

SPRINGERNATURE

ISSN

0007-0920

eISSN

1532-1827
1532-1827

Collections

Genetics and Epidemiology

Research Team

Cancer Genomics

Notes