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

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 a...

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Detalles Bibliográficos
Autores: Barahona Ponce, Carol, Scherer, Dominique, Brinster, Regina, Boekstegers, Felix, Marcelain, Katherine, Gárate Calderón, Valentina, Müller, Bettina, de Toro, Gonzalo, Retamales, Javier, Barajas, Olga, Ahumada, Monica, Morales, Erik, Rojas, Armando, Sanhueza, Verónica, Loader, Denisse, Rivera, María Teresa, Gutiérrez, Lorena, Bernal, Giuliano, Ortega, Alejandro, Montalvo, Domingo, Portiño, Sergio, Bertrán, Maria Enriqueta, Gabler, Fernando, Spencer, Loreto, Olloquequi, Jordi, Fischer, Christine, Jenab, Mazda, Aleksandrova, Krasimira, Katzke, Verena, Gonzalez-Jose, Rolando
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/152388
Acceso en línea:http://hdl.handle.net/11336/152388
Access Level:acceso abierto
Palabra clave:POBLACIONES MESTIZAS
CANCER DE VESÍCULA
LATINOAMÉRICA
GENÓMICA
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario: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. (Hepatology 2021;73:1783-1796).

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