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Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis
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Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis
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Journal Article
Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis
2021
Overview
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 (OR
SD
) 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 (OR
SD
= 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Calculi
/ Cholelithiasis - complications
/ Cholelithiasis - epidemiology
/ Colorectal Neoplasms - complications
/ Colorectal Neoplasms - epidemiology
/ Colorectal Neoplasms - genetics
/ Genetic Predisposition to Disease
/ Genome-Wide Association Study
/ Humans
/ Mendelian Randomization Analysis
/ Oncology
