Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis.
Date
2021-03-16Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Cholelithiasis
Colorectal Neoplasms
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Prognosis
Risk Factors
United Kingdom
Research team
Cancer Genomics
Language
eng
Date accepted
2020-11-25
License start date
2021-01-07
Citation
British Journal of Cancer, 2021, 124 (6), pp. 1169 - 1174
Publisher
SPRINGERNATURE