Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis.
Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis.
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胆结石疾病和胆红素水平与结直肠癌风险之间缺乏关联：孟德尔随机分析
DOI：
10.1038/s41416-020-01211-x
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发表时间：
2021-03
影响因子：
8.8
通讯作者：
Houlston RS
中科院分区：
文献类型：
--
作者：
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
胆结石疾病和循环胆红素水平与结直肠癌（CRC）发生风险之间关系的流行病学研究一直不一致。为了解决可能的混淆和反向因果关系，我们使用孟德尔随机化（MR）检查了这些潜在危险因素与CRC之间的关系。我们在26397例结直肠癌患者和41481例对照中使用双样本MR检查了胆结石疾病遗传易感性和循环胆红素水平之间的关系。我们计算了结直肠癌中对数胆红素水平（ORSD）每遗传预测SD单位增加的比值比，并测试了胆结石对结直肠癌的非零因果效应。灵敏度分析用于识别估计器假设的违反情况。胆结石疾病（P值= 0.60）或循环胆红素水平（ORSD = 1.00, 95%可信区间(CI) = 0.96-1.03， P值= 0.90）与结直肠癌均无相关性。尽管这项研究的规模很大，但我们没有发现循环胆红素水平或胆结石疾病与发生结直肠癌风险之间存在因果关系的证据。虽然一些观察性研究表明的影响程度可以有把握地排除，但我们不能排除较小效应大小和非线性关系的可能性。
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). 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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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
全基因组关联荟萃分析产生了20个与胆结石疾病相关的基因座。
影响因子：
16.6
作者：
Ferkingstad E;Oddsson A;Gretarsdottir S;Benonisdottir S;Thorleifsson G;Deaton AM;Jonsson S;Stefansson OA;Norddahl GL;Zink F;Arnadottir GA;Gunnarsson B;Halldorsson GH;Helgadottir A;Jensson BO;Kristjansson RP;Sveinbjornsson G;Sverrisson DA;Masson G;Olafsson I;Eyjolfsson GI;Sigurdardottir O;Holm H;Jonsdottir I;Olafsson S;Steingrimsdottir T;Rafnar T;Bjornsson ES;Thorsteinsdottir U;Gudbjartsson DF;Sulem P;Stefansson K
通讯作者：
Stefansson K
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S