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Gallstones, body mass index, C-reactive protein, and gallbladder cancer: Mendelian randomization analysis of Chilean and European genotype data

dc.contributor.authorBarahona-Ponce, Carol
dc.contributor.authorScherer, Dominique
dc.contributor.authorBrinster, Regina
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorGárate-Calderón, Valentina
dc.contributor.authorMüller, Bettina
dc.contributor.authorDe Toro, Gonzalo
dc.contributor.authorRetamales, Javier
dc.contributor.authorBarajas, Olga
dc.contributor.authorAhumada, Monica
dc.contributor.authorMorales, Erik
dc.contributor.authorRojas, Armando
dc.contributor.authorSanhueza, Verónica
dc.contributor.authorLoader, Denisse
dc.contributor.authorRivera, María T.
dc.contributor.authorGutiérrez, Lorena
dc.contributor.authorBernal, Giuliano
dc.contributor.authorOrtega, Alejandro
dc.contributor.authorMontalvo, Domingo
dc.contributor.authorPortiño, Sergio
dc.contributor.authorBertrán, María E.
dc.contributor.authorGabler, F.
dc.contributor.authorSpencer, Loreto
dc.contributor.authorOlloquequi, Jordi
dc.contributor.authorFischer, Christine
dc.contributor.authorJenab, Mazda
dc.contributor.authorAleksandrova, Krasimira
dc.contributor.authorKatzke, Verena
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorBonet, Catalina
dc.contributor.authorMoradi, Tahereh
dc.contributor.authorFischer, Krista
dc.contributor.authorBossers, Willem
dc.contributor.authorBrenner, Hermann
dc.contributor.authorHveem, Kristian
dc.contributor.authorEklund, Niina
dc.contributor.authorVölker, Uwe
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorFuentes-Guajardo, Macarena
dc.contributor.authorGonzález-José, Rolando
dc.contributor.authorBedoya, Gabriel
dc.contributor.authorBortolini, María C.
dc.contributor.authorCanizales, Samuel
dc.contributor.authorGallo, Carla
dc.contributor.authorRuiz-Linares, Andres
dc.contributor.authorRothhammer, Francisco
dc.contributor.authorLorenzo-Bermejo, Justo
dc.date.accessioned2021-12-30T14:51:54Z
dc.date.available2021-12-30T14:51:54Z
dc.date.issued2021
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/3682
dc.description.abstractBackground and Aims: Gallbladder 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 programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. Approach and Results: 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. Conclusions: Two risk factors considered in the current Chilean program 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.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceHepatology, 73(5), 1783-1796es_CL
dc.titleGallstones, body mass index, C-reactive protein, and gallbladder cancer: Mendelian randomization analysis of Chilean and European genotype dataes_CL
dc.typeArticlees_CL
dc.ucm.facultadFacultad de Medicinaes_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.uriaasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31537es_CL
dc.ucm.doidoi.org/10.1002/hep.31537es_CL


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