TY - JOUR
T1 - Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer
T2 - Mendelian Randomization Analysis of Chilean and European Genotype Data
AU - Barahona Ponce, Carol
AU - Scherer, Dominique
AU - Brinster, Regina
AU - Boekstegers, Felix
AU - Marcelain, Katherine
AU - Gárate-Calderón, Valentina
AU - Müller, Bettina
AU - de Toro, Gonzalo
AU - Retamales, Javier
AU - Barajas, Olga
AU - Ahumada, Monica
AU - Morales, Erik
AU - Rojas, Armando
AU - Sanhueza, Verónica
AU - Loader, Denisse
AU - Rivera, María Teresa
AU - Gutiérrez, Lorena
AU - Bernal, Giuliano
AU - Ortega, Alejandro
AU - Montalvo, Domingo
AU - Portiño, Sergio
AU - Bertrán, Maria Enriqueta
AU - Gabler, Fernando
AU - Spencer, Loreto
AU - Olloquequi, Jordi
AU - Fischer, Christine
AU - Jenab, Mazda
AU - Aleksandrova, Krasimira
AU - Katzke, Verena
AU - Weiderpass, Elisabete
AU - Bonet, Catalina
AU - Moradi, Tahereh
AU - Fischer, Krista
AU - Bossers, Willem
AU - Brenner, Hermann
AU - Hveem, Kristian
AU - Eklund, Niina
AU - Völker, Uwe
AU - Waldenberger, Melanie
AU - Fuentes Guajardo, Macarena
AU - Gonzalez-Jose, Rolando
AU - Bedoya, Gabriel
AU - Bortolini, Maria C.
AU - Canizales-Quinteros, Samuel
AU - Gallo, Carla
AU - Ruiz-Linares, Andres
AU - Rothhammer, Francisco
AU - Lorenzo Bermejo, Justo
N1 - Publisher Copyright:
© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85104970954
U2 - 10.1002/hep.31537
DO - 10.1002/hep.31537
M3 - Artículo
C2 - 32893372
AN - SCOPUS:85104970954
SN - 0270-9139
VL - 73
SP - 1783
EP - 1796
JO - Hepatology
JF - Hepatology
IS - 5
ER -
SDG 3 Good Health and Well-being