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000163033 0247_ $$2doi$$adoi: 10.1002/hep.31537.
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000163033 1001_ $$aBarahona Ponce, Carol$$b0
000163033 245__ $$aGallstones, Body Mass Index, C-reactive Protein and Gallbladder Cancer - Mendelian Randomization Analysis of Chilean and European Genotype Data.
000163033 260__ $$aNew York [u.a.]$$bWiley Interscience$$c2021
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000163033 500__ $$a2021 May;73(5):1783-1796
000163033 520__ $$aGallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here we investigate the causal effects of risk factors considered in current GBC prevention programmes as well as C-reactive protein (CRP) level as a marker of chronic inflammation.We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (p = 9 × 10-5 ) and Europeans (p = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (p = 0.03), while higher CRP concentrations increased GBC risk in Europeans (p = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (p = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors.Two risk factors considered in the current Chilean programme for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
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000163033 7001_ $$aScherer, Dominique$$b1
000163033 7001_ $$aBrinster, Regina$$b2
000163033 7001_ $$00000-0002-0587-7624$$aBoekstegers, Felix$$b3
000163033 7001_ $$aMarcelain, Katherine$$b4
000163033 7001_ $$aGárate, Valentina$$b5
000163033 7001_ $$aMüller, Bettina$$b6
000163033 7001_ $$ade Toro, Gonzalo$$b7
000163033 7001_ $$aRetamales, Javier$$b8
000163033 7001_ $$aBarajas, Olga$$b9
000163033 7001_ $$aAhumada, Monica$$b10
000163033 7001_ $$aMorales, Erik$$b11
000163033 7001_ $$aRojas, Armando$$b12
000163033 7001_ $$aSanhueza, Verónica$$b13
000163033 7001_ $$aLoader, Denisse$$b14
000163033 7001_ $$aRivera, María Teresa$$b15
000163033 7001_ $$aGutiérrez, Lorena$$b16
000163033 7001_ $$aBernal, Giuliano$$b17
000163033 7001_ $$aOrtega, Alejandro$$b18
000163033 7001_ $$aMontalvo, Domingo$$b19
000163033 7001_ $$aPortiño, Sergio$$b20
000163033 7001_ $$aBertrán, Maria Enriqueta$$b21
000163033 7001_ $$aGabler, Fernando$$b22
000163033 7001_ $$aSpencer, Loreto$$b23
000163033 7001_ $$aOlloquequi, Jordi$$b24
000163033 7001_ $$aFischer, Christine$$b25
000163033 7001_ $$aJenab, Mazda$$b26
000163033 7001_ $$aAleksandrova, Krasimira$$b27
000163033 7001_ $$0P:(DE-He78)fb68a9386399d72d84f7f34cfc6048b4$$aKatzke, Verena$$b28$$udkfz
000163033 7001_ $$00000-0003-2237-0128$$aWeiderpass, Elisabete$$b29
000163033 7001_ $$aBonet, Catalina$$b30
000163033 7001_ $$aMoradi, Tahereh$$b31
000163033 7001_ $$aFischer, Krista$$b32
000163033 7001_ $$aBossers, Willem$$b33
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000163033 7001_ $$aHveem, Kristian$$b35
000163033 7001_ $$aEklund, Niina$$b36
000163033 7001_ $$aVölker, Uwe$$b37
000163033 7001_ $$aWaldenberger, Melanie$$b38
000163033 7001_ $$aFuentes Guajardo, Macarena$$b39
000163033 7001_ $$aGonzalez-Jose, Rolando$$b40
000163033 7001_ $$aBedoya, Gabriel$$b41
000163033 7001_ $$aBortolini, Maria C$$b42
000163033 7001_ $$aCanizales, Samuel$$b43
000163033 7001_ $$aGallo, Carla$$b44
000163033 7001_ $$aRuiz Linares, Andres$$b45
000163033 7001_ $$aRothhammer, Francisco$$b46
000163033 7001_ $$aLorenzo Bermejo, Justo$$b47
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