Universidad Peruana Cayetano Heredia

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data

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dc.contributor.author Barahona Ponce, Carol
dc.contributor.author Scherer, Dominique
dc.contributor.author Brinster, Regina
dc.contributor.author Boekstegers, Felix
dc.contributor.author Marcelain, Katherine
dc.contributor.author Gárate-Calderón, Valentina
dc.contributor.author Müller, Bettina
dc.contributor.author de Toro, Gonzalo
dc.contributor.author Retamales, Javier
dc.contributor.author Barajas, Olga
dc.contributor.author Ahumada, Monica
dc.contributor.author Morales, Erik
dc.contributor.author Rojas, Armando
dc.contributor.author Sanhueza, Verónica
dc.contributor.author Loader, Denisse
dc.contributor.author Rivera, María Teresa
dc.contributor.author Gutiérrez, Lorena
dc.contributor.author Bernal, Giuliano
dc.contributor.author Ortega, Alejandro
dc.contributor.author Montalvo, Domingo
dc.contributor.author Portiño, Sergio
dc.contributor.author Bertrán, Maria Enriqueta
dc.contributor.author Gabler, Fernando
dc.contributor.author Spencer, Loreto
dc.contributor.author Olloquequi, Jordi
dc.contributor.author Fischer, Christine
dc.contributor.author Jenab, Mazda
dc.contributor.author Aleksandrova, Krasimira
dc.contributor.author Katzke, Verena
dc.contributor.author Weiderpass, Elisabete
dc.contributor.author Bonet, Catalina
dc.contributor.author Moradi, Tahereh
dc.contributor.author Fischer, Krista
dc.contributor.author Bossers, Willem
dc.contributor.author Brenner, Hermann
dc.contributor.author Hveem, Kristian
dc.contributor.author Eklund, Niina
dc.contributor.author Völker, Uwe
dc.contributor.author Waldenberger, Melanie
dc.contributor.author Fuentes Guajardo, Macarena
dc.contributor.author Gonzalez-Jose, Rolando
dc.contributor.author Bedoya, Gabriel
dc.contributor.author Bortolini, Maria C.
dc.contributor.author Canizales-Quinteros, Samuel
dc.contributor.author Gallo López-Aliaga, Carla Maria
dc.contributor.author Ruiz-Linares, Andres
dc.contributor.author Rothhammer, Francisco
dc.contributor.author Lorenzo Bermejo, Justo
dc.date.accessioned 2021-05-18T21:44:15Z
dc.date.available 2021-05-18T21:44:15Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/20.500.12866/9374
dc.description.abstract BACKGROUND 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 en_US
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartofseries Hepatology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Gallstones en_US
dc.subject Body Mass Index en_US
dc.subject C-Reactive Protein en_US
dc.subject Gallbladder Cancer en_US
dc.subject Chile en_US
dc.title Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1002/hep.31537
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.19
dc.relation.issn 1527-3350


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