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000166716 1001_ $$00000-0003-4534-9241$$aCulliford, Richard$$b0
000166716 245__ $$aLack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis.
000166716 260__ $$aEdinburgh$$bNature Publ. Group$$c2021
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000166716 500__ $$a2021 Mar;124(6):1169-1174
000166716 520__ $$aEpidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR).We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions.No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96-1.03, P value = 0.90) with CRC was shown.Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.
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000166716 7001_ $$00000-0002-3966-3501$$aCornish, Alex J$$b1
000166716 7001_ $$aLaw, Philip J$$b2
000166716 7001_ $$aFarrington, Susan M$$b3
000166716 7001_ $$aPalin, Kimmo$$b4
000166716 7001_ $$aJenkins, Mark A$$b5
000166716 7001_ $$aCasey, Graham$$b6
000166716 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b7$$udkfz
000166716 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b8$$udkfz
000166716 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b9$$udkfz
000166716 7001_ $$aKirac, Iva$$b10
000166716 7001_ $$aMaughan, Tim$$b11
000166716 7001_ $$aBrezina, Stefanie$$b12
000166716 7001_ $$aGsur, Andrea$$b13
000166716 7001_ $$aCheadle, Jeremy P$$b14
000166716 7001_ $$aAaltonen, Lauri A$$b15
000166716 7001_ $$aDunlop, Malcom G$$b16
000166716 7001_ $$aHoulston, Richard S$$b17
000166716 773__ $$0PERI:(DE-600)2002452-6$$a10.1038/s41416-020-01211-x$$n6$$p1169-1174$$tBritish journal of cancer$$v124$$x1532-1827$$y2021
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