Periodic Reporting for period 2 - EULAT Eradicate GBC (Establishment and Exploitation of a European-Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer)
Periodo di rendicontazione: 2021-06-01 al 2022-11-30
Gallbladder cancer (GBC) is a neglected disease with huge potential for prevention. This project aims at significantly improving the accuracy of risk estimation and early detection of GBC by identifying and adequately considering geographical, environmental, lifestyle, ethnic, gender and molecular differences. We plan to generate the information needed to establish and refine current prevention programmes, including the primary, secondary and tertiary prevention of GBC. We will (1) build a unique European–Latin American GBC biorepository integrated into a tailored IT platform, (2) identify, validate and functionally characterize novel GBC biomarkers, (3) develop a multifactorial risk score that integrates established and newly identified epidemiological and molecular risk factors, (4) improve the understanding of the causal mechanisms that link lifestyle, cultural and behavioural factors to GBC development, (5) unravel novel opportunities for the targeted therapy of incidental GBC, (6) exploit existing and newly generated epidemiological and multi-omics data to improve the accuracy of GBC risk prediction and (7) contribute to the training of the next generation of Latin American researchers in precision medicine for GBC. The generated information will permit identification of individuals at high GBC risk, guiding surveillance and individual decisions on the possible benefit of preventive gallbladder removal in regions of low and high GBC incidence. Novel data on genomic alterations in incidental GBC will pave the way towards implementation of future clinical trials. The planned European–Latin American GBC biorepository and IT platform will constitute a prime resource for translational research on individualized prevention, personalized early detection and targeted therapy of GBC. The participation in our project of representatives of health authorities, patients and the industry guarantees the efficient incorporation of project results into national health policies.
Work Package 1
By 30 November 2022, 4,160 patients had been recruited. The corresponding samples were processed and stored, and clinical as well as demographic and epidemiological data were collected.
The harmonization across the recruitment sites included (a) an online training course for study nurses and selected PhD students; (b) the development of a biobank handbook; (c) the development, validation and use of technical operational guidelines, prepared by the Biobank of Universidad de Chile in close collaboration with the Biobank of the National Center for Tumor Diseases in Heidelberg, Germany, and the Latin American project manager; (d) a programme for quality assurance, quality control and standardised data management and (e) the development of a computer application for the patient interviews, sample information, case report forms and a food frequency questionnaire. We have also developed and validated computer scripts for automated generation of sample inventories and close monitoring of the recruitment rates and data quality at each recruitment site. We are using these materials to train the personnel who recruits the patients and processes the samples at new (contingency) sites.
Work package 2
Extensive discussions were held with worldwide experts in the field to optimize sample use and generate high quality metabolomics and proteomics data (markers of gut barrier function).
Samples from European GBC cases and matched controls were submitted for measurement of circulating metabolites and proteins reflecting gut barrier function. The food frequency questionnaire (FFQ) implemented in the EULAT eCollect application was validated and tested under real-world conditions.
Work package 3
Small non-coding (snc)RNA-sequencing data were generated for serum and plasma case-control sample pairs from the large European prospective cohorts.
Work package 4
This work package will start in month 37 of the project. The necessary FFPE samples have been collected and we are finalising DNA and RNA extraction.
Work package 5
We are developing web-based tools to make it easier for interested scientists to search the aggregated data generated by the project. A pilot has been carried out to test the functionality and use of the platform.
Work package 6
Four Latin American and one European PhD students have been recruited. We organized the advanced courses Introduction to Mendelian randomization and Biostatistical Analysis of Genotype Data, as well as the symposium Native American Ancestry in Genetic Research Projects.
Work package 7
The Executive Board, External Advisory Board, Project Management Office and Data Management Plan of EULAT Eradicate GBC have been established. The annual meeting of EULAT Eradicate GBC took place online on 20 November 2021.
Work package 8
The EULAT Eradicate GBC project meets all ethical requirements as outlined in the submitted deliverables.
By 30 November 2022, 4,160 patients had been recruited. The corresponding samples were processed and stored, and clinical as well as demographic and epidemiological data were collected.
The harmonization across the recruitment sites included (a) an online training course for study nurses and selected PhD students; (b) the development of a biobank handbook; (c) the development, validation and use of technical operational guidelines, prepared by the Biobank of Universidad de Chile in close collaboration with the Biobank of the National Center for Tumor Diseases in Heidelberg, Germany, and the Latin American project manager; (d) a programme for quality assurance, quality control and standardised data management and (e) the development of a computer application for the patient interviews, sample information, case report forms and a food frequency questionnaire. We have also developed and validated computer scripts for automated generation of sample inventories and close monitoring of the recruitment rates and data quality at each recruitment site. We are using these materials to train the personnel who recruits the patients and processes the samples at new (contingency) sites.
Work package 2
Extensive discussions were held with worldwide experts in the field to optimize sample use and generate high quality metabolomics and proteomics data (markers of gut barrier function).
Samples from European GBC cases and matched controls were submitted for measurement of circulating metabolites and proteins reflecting gut barrier function. The food frequency questionnaire (FFQ) implemented in the EULAT eCollect application was validated and tested under real-world conditions.
Work package 3
Small non-coding (snc)RNA-sequencing data were generated for serum and plasma case-control sample pairs from the large European prospective cohorts.
Work package 4
This work package will start in month 37 of the project. The necessary FFPE samples have been collected and we are finalising DNA and RNA extraction.
Work package 5
We are developing web-based tools to make it easier for interested scientists to search the aggregated data generated by the project. A pilot has been carried out to test the functionality and use of the platform.
Work package 6
Four Latin American and one European PhD students have been recruited. We organized the advanced courses Introduction to Mendelian randomization and Biostatistical Analysis of Genotype Data, as well as the symposium Native American Ancestry in Genetic Research Projects.
Work package 7
The Executive Board, External Advisory Board, Project Management Office and Data Management Plan of EULAT Eradicate GBC have been established. The annual meeting of EULAT Eradicate GBC took place online on 20 November 2021.
Work package 8
The EULAT Eradicate GBC project meets all ethical requirements as outlined in the submitted deliverables.
The direct results (scientific publications, PhD training, advanced courses, … ) of the ongoing project activities (patient recruitment, molecular characterisation of collected samples, data analysis, project management, …) are advancing scientific knowledge to create new research capacities, to refine GBC prevention strategies and to improve health policies in the medium and long term. We would like to highlight the following immediate impacts of EULAT Eradicate GBC:
a. Advancing knowledge. The developed computer application can be easily adapted and reused by other projects. The same applies to the implemented training course for recruitment staff, the developed and validated operational guidelines, and our tested instruments for project management. To disseminate the developed application (EULAT eCollect) for electronic collection of socio-demographic, clinical, lifestyle, dietary, and sample-related information within EULAT Eradicate GBC, we published the article Development of an Application for Electronic Retrieval of Patient and Sample Information in Latin American Regions with a High Incidence of Gallbladder Cancer in the special issue Personalized Prevention of Gallbladder Cancer of the Journal of Personalized Medicine (https://www.mdpi.com/2075-4426/12/9/1476).
b. Capacity building and research targeting. EULAT Eradicate GBC is positively influencing the development and enhancement of research skills in individuals and teams, including more than ten study nurses, ten clinicians, four research technicians and five PhD students (four from Latin America and one from the UK), four Masters students and four postdoctoral fellows, two junior researchers and 13 senior researchers from Europe and Latin America. Complementary funding has been successfully acquired.
c. Informing decision making, practice and policy. We are in regular contact with representatives of the Chilean Ministry of Health.
d. Population health and health sector benefits. We collaborate actively with the Chilean Foundation of Gastrointestinal Cancer Patients (https://gist.cl/2019/12/17/gist-chile-contribuye-al-proyecto-eulat-eradicate-gbc/) to improve the transfer and communication of the outputs of the project. The EULAT Eradicate GBC dissemination videos are also available in Native American languages such as Aymara, Quechua and Mapudungun, the language of the Mapuche people (https://youtu.be/HsPeid1Rmus) and our manuscripts with ethnic aspects are reviewed by experts in Mapuche culture prior to submission.
a. Advancing knowledge. The developed computer application can be easily adapted and reused by other projects. The same applies to the implemented training course for recruitment staff, the developed and validated operational guidelines, and our tested instruments for project management. To disseminate the developed application (EULAT eCollect) for electronic collection of socio-demographic, clinical, lifestyle, dietary, and sample-related information within EULAT Eradicate GBC, we published the article Development of an Application for Electronic Retrieval of Patient and Sample Information in Latin American Regions with a High Incidence of Gallbladder Cancer in the special issue Personalized Prevention of Gallbladder Cancer of the Journal of Personalized Medicine (https://www.mdpi.com/2075-4426/12/9/1476).
b. Capacity building and research targeting. EULAT Eradicate GBC is positively influencing the development and enhancement of research skills in individuals and teams, including more than ten study nurses, ten clinicians, four research technicians and five PhD students (four from Latin America and one from the UK), four Masters students and four postdoctoral fellows, two junior researchers and 13 senior researchers from Europe and Latin America. Complementary funding has been successfully acquired.
c. Informing decision making, practice and policy. We are in regular contact with representatives of the Chilean Ministry of Health.
d. Population health and health sector benefits. We collaborate actively with the Chilean Foundation of Gastrointestinal Cancer Patients (https://gist.cl/2019/12/17/gist-chile-contribuye-al-proyecto-eulat-eradicate-gbc/) to improve the transfer and communication of the outputs of the project. The EULAT Eradicate GBC dissemination videos are also available in Native American languages such as Aymara, Quechua and Mapudungun, the language of the Mapuche people (https://youtu.be/HsPeid1Rmus) and our manuscripts with ethnic aspects are reviewed by experts in Mapuche culture prior to submission.