Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high‐incidence country

Author:

Boekstegers Felix1ORCID,Scherer Dominique1ORCID,Barahona Ponce Carol1ORCID,Marcelain Katherine2ORCID,Gárate‐Calderón Valentina12,Waldenberger Melanie3,Morales Erik45,Rojas Armando5,Munoz César45,Retamales Javier6,de Toro Gonzalo78,Barajas Olga29,Rivera María Teresa10,Cortés Analía10,Loader Denisse11,Saavedra Javiera11,Gutiérrez Lorena12,Ortega Alejandro13,Bertrán Maria Enriqueta14,Bartolotti Leonardo15,Gabler Fernando16,Campos Mónica16,Alvarado Juan17,Moisán Fabricio17,Spencer Loreto17,Nervi Bruno18ORCID,Carvajal‐Hausdorf Daniel19,Losada Héctor20,Almau Mauricio21,Fernández Plinio21,Olloquequi Jordi2223,Fuentes‐Guajardo Macarena24,Gonzalez‐Jose Rolando25,Bortolini Maria Cátira26,Acuña‐Alonzo Victor27,Gallo Carla28,Linares Andres Ruiz293031,Rothhammer Francisco32,Lorenzo Bermejo Justo133ORCID

Affiliation:

1. Statistical Genetics Research Group, Institute of Medical Biometry Heidelberg University Heidelberg Germany

2. Department of Basic and Clinical Oncology, Medical Faculty University of Chile Santiago Chile

3. Research Unit of Molecular Epidemiology and Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

4. Hospital Regional de Talca Talca Chile

5. Facultad de Medicina Universidad Católica del Maule Talca Chile

6. Instituto Nacional del Cáncer Santiago Chile

7. Hospital de Puerto Montt Puerto Montt Chile

8. Escuela de Tecnología Médica Universidad Austral de Chile sede Puerto Montt Puerto Montt Chile

9. Hospital Clínico Universidad de Chile Santiago Chile

10. Hospital del Salvador Santiago Chile

11. Hospital Padre Hurtado Santiago Chile

12. Hospital San Juan de Dios Santiago Chile

13. Hospital Regional Arica Chile

14. Unidad Registro Hospitalario de Cáncer Hospital Base de Valdivia Valdivia Chile

15. Hospital Base de Valdivia Chile

16. Hospital San Borja Arriarán Santiago Chile

17. Hospital Regional Guillermo Grant Benavente Concepción Chile

18. Departamento de Hematología y Oncología Escuela de Medicina Pontificia Universidad Católica de Chile Santiago Chile

19. Facultad de Medicina Clínica Alemana, Universidad del Desarrollo Santiago Chile

20. Departamento de Cirugía Universidad de La Frontera Temuco Chile

21. Hospital de Rancagua Rancagua Chile

22. Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences University of Barcelona Barcelona Spain

23. Facultad de Ciencias de la Salud Universidad Autónoma de Chile Talca Chile

24. Departamento de Tecnología Médica, Facultad de Ciencias de la Salud Tarapacá University Arica Chile

25. Instituto Patagónico de Ciencias Sociales y Humanas Centro Nacional Patagónico, CONICET Puerto Madryn Argentina

26. Departamento de Genética, Instituto de Biociências Universidad Federal do Rio Grande do Sul Porto Alegre Brazil

27. National Institute of Anthropology and History Mexico City Mexico

28. Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Universidad Peruana Cayetano Heredia Lima Peru

29. 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

30. Aix‐Marseille Université, CNRS, EFS, ADES Marseille France

31. Department of Genetics, Evolution and Environment, and UCL Genetics Institute University College London London UK

32. Instituto de Alta Investigación Tarapacá University Arica Chile

33. Department of Biostatistics for Precision Oncology Institut de Cancérologie Strasbourg Europe Strasbourg France

Abstract

AbstractSince 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population‐based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non‐genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision‐recall curve (AUC‐PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC‐PRC for the Baseline Model (0.44%, 95%CI 0.42‐0.46) increased by 0.22 (95%CI 0.15‐0.29) when non‐genetic factors were included, and by 0.25 (95%CI 0.20‐0.30) when incorporating non‐genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104‐131) decreased to 92 (95%CI 60‐128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59‐110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non‐genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Funder

Horizon 2020 Framework Programme

Universidad de Chile

Deutsche Forschungsgemeinschaft

Publisher

Wiley

Subject

Cancer Research,Oncology

Reference21 articles.

1. Health Ministry of Chile.Problema de Salud AUGE N 26. Cholecistectomía Preventiva Del cáncer De Vésicula En Personas De 35 a 49 años 2015.

2. Coverage of the gallbladder cancer prevention strategy in Chile: results from the 2009–2010 National Health Survey;Latorre SG;Revista medica de Chile,2015

3. Health Ministry of Chile: Department of Statistics and Health Information in Chile.Data publically available.https://deis.minsal.cl/

4. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement

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