Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data
MetadataShow full item record
Barahona Ponce, Carol
Müller, Bettina G.
de Toro, Gonzalo
Rojas R., Armando
Rivera, María Teresa
Bertrán, Maria Enriqueta
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.
Showing items related by title, author, creator and subject.
Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data (2021) Barahona Ponce, Carol; Scherer, Dominique; Brinster, Regina; Boekstegers, Felix; Marcelain, Katherine; Gárate-Calderón, Valentina; Müller, Bettina G.; de Toro, Gonzalo; Retamales, Javier; Barajas, Olga; ... (John Wiley and Sons Inc, 2021-05)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 ...
Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression (2022) Blandino, Alice; Scherer, Dominique; Rounge, Trine Ballestad; Umu, Sinan UÄŸur; Boekstegers, Felix; Barahona Ponce, Carol; Marcelain, Katherine; Gárate-Calderón, Valentina; Waldenberger, Melanie; Morales, Erik; ... (MDPI, 2022-02-01)Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candi-dates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we ...
ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans (2020) Boekstegers F.; Marcelain K.; Barahona Ponce C.; Baez Benavides P.F.; Müller B.; de Toro G.; Retamales J.; Barajas O.; Ahumada M.; Morales E.; ... (Elsevier Ltd, 2020)