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

Autor: Barahona Ponce C; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago de Chile, Chile., Scherer D; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany., Brinster R; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany., Boekstegers F; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany., Marcelain K; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago de Chile, Chile., Gárate-Calderón V; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago de Chile, Chile., Müller B; Servicio de Oncología Médica, Instituto Nacional del Cáncer, Santiago, Chile., de Toro G; Escuela de Tecnologia Medica, Universidad Austral de Chile sede Puerto Montt, Puerto Montt, Chile.; Servicio de Anatomía Patológica, Hospital de Puerto Montt, Puerto Montt, Chile., Retamales J; Servicio de Oncología Médica, Instituto Nacional del Cáncer, Santiago, Chile., Barajas O; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago de Chile, Chile.; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago, Chile.; Oncology Department, Hospital Clínico Universidad de Chile, Santiago, Chile., Ahumada M; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago de Chile, Chile.; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago, Chile.; Oncology Department, Hospital Clínico Universidad de Chile, Santiago, Chile., Morales E; Facultad de Medicina, Universidad Católica del Maule, Talca, Chile.; Unidad de Anatomía Patológica del Hospital Regional de Talca, Talca, Chile., Rojas A; Laboratorio de Investigaciones Biomédicas en la Facultad de Medicina, Universidad Católica del Maule, Talca, Chile., Sanhueza V; Servicio de Anatomía Patológica, Hospital Padre Hurtado, Santiago, Chile., Loader D; Servicio de Anatomía Patológica, Hospital Padre Hurtado, Santiago, Chile., Rivera MT; Servicio de Anatomía Patológica, Hospital del Salvador, Santiago, Chile., Gutiérrez L; Servicio de Anatomía Patológica, Hospital San Juan de Dios, Santiago, Chile., Bernal G; Laboratory of Molecular and Cellular Biology of Cancer (CancerLab), Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile., Ortega A; Servicio de Anatomía Patológica, Hospital Regional, Arica, Chile., Montalvo D; Department of Surgery, Hospital Juan Noe Crevani, Arica, Chile., Portiño S; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Santiago, Chile.; Oncology Department, Hospital Clínico Universidad de Chile, Santiago, Chile., Bertrán ME; Secretaría Regional Ministerial de Salud, Ministerio de Salud, Valdivia, Chile., Gabler F; Servicio de Anatomía Patológica, Hospital San Borja Arriarán, Santiago, Chile., Spencer L; Servicio de Anatomía Patológica, Hospital Regional Guillermo Grant Benavente, Concepción, Chile., Olloquequi J; Laboratory of Cellular and Molecular Pathology, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile., Fischer C; Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany., Jenab M; International Agency for Research on Cancer, Lyon, France., Aleksandrova K; Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany., Katzke V; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany., Weiderpass E; International Agency for Research on Cancer, World Health Organization, Lyon, France., Bonet C; Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain., Moradi T; Division of Epidemiology, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Fischer K; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia., Bossers W; The Lifelines Cohort Study, Groningen, Netherlands., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center, National Center for Tumor Diseases, Heidelberg, Germany.; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany., Hveem K; The Nord-Trøndelag Health Research Centre, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Public Health and Nursing, K.G. Jebsen Centre for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway., Eklund N; Genomics and Biobank, National Institute for Health and Welfare, Helsinki, Finland., Völker U; Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Universitätsmedizin Greifswald, Germany., Waldenberger M; Research Unit of Molecular Epidemiology and Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Fuentes Guajardo M; Instituto de Alta Investigación, Tarapacá University, Arica, Chile., Gonzalez-Jose R; Centro Nacional Patagónico, Instituto Patagónico de Ciencias Sociales y Humanas, CONICET, Puerto Madryn, Argentina., Bedoya G; Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia., Bortolini MC; Instituto de Biociências, Universidad Federal do Rio Grande do Sul, Puerto Alegre, Brazil., Canizales-Quinteros S; Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México., Gallo C; Unidad de Neurobiología Molecular y Genética, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru., Ruiz-Linares A; Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.; Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France.; Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, UK., Rothhammer F; Instituto de Alta Investigación, Tarapacá University, Arica, Chile., Lorenzo Bermejo J; Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Hepatology (Baltimore, Md.) [Hepatology] 2021 May; Vol. 73 (5), pp. 1783-1796.
DOI: 10.1002/hep.31537
Abstrakt: 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.
(© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
Databáze: MEDLINE
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