Establishment and Exploitation of a European-Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer

Project Information

EULAT Eradicate GBC

Grant agreement ID: 825741

DOI

10.3030/825741

EC signature date 21 August 2019

Start date 1 December 2019

End date 30 November 2026

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 4 675 932,30

EU contribution

€ 4 675 932,30

Coordinated by

UNIVERSITATSKLINIKUM HEIDELBERG
Germany

Periodic Reporting for period 3 - EULAT Eradicate GBC (Establishment and Exploitation of a European-Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer)

Reporting period: 2022-12-01 to 2024-05-31

Summary of the context and overall objectives of the project

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 performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

WP 1
By 31 May 2024, 9,008 patients had been recruited. The corresponding samples were processed and stored, and clinical as well as demographic and epidemiological data were collected. Series A of samples was shipped to the coordinating center (UKHD), while Series B remains at the recruitment centers for research of the local PIs.

The harmonization across the recruitment sites included (a) online training course for study nurses and PhD students, (b) development of a biobank handbook, (c) 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 program for quality assurance, quality control and standardized data management and (e) the development of a computer application for the patient interviews, sample information, CRFs and FFQ. Computer scripts for automated generation of sample inventories and close monitoring of the recruitment rates and data quality at each recruitment site were established. We are using these materials to train the personnel who recruits the patients and processes the samples at new (contingency) sites.

The large European prospective cohorts were re-contacted to apply for additional samples. The collection of GBC cases and controls according to EULAT Eradicate GBC SOPs was initiated at the Institut de cancérologie Strasbourg Europe (ICANS), where the project coordinator, Prof. Justo Lorenzo Bermejo, has a part-time position.

WP 2
Data harmonization steps have been established.
Circulating metabolites and proteins reflecting gut barrier function were measured in samples from European GBC cases and matched controls, and initial statistical analyses were performed.
The FFQ implemented in the EULAT eCollect application was applied in Latin America, and initial statistical analyses were performed.

WP 3
Small non-coding (snc)RNA-sequencing data were generated for the European study population and statistical analyses have been performed.
Latin American samples were sent to the Norwegian partner for sncRNA sequencing.

WP 4
FFPE sample collection and DNA/RNA extraction continue.
Using existing data, somatic mutations have been analyzed in 56 GBC samples.
An ARID1A Knock-out cell line is being established.

WP 5
We are developing web-based tools to make it easier for interested scientists to search the aggregated data generated by the project.
Several biomarkers (e.g. sncRNA, metals) and demographic risk factors (e.g. ancestry proportion) are under investigation for their association with GBC risk. We have identified miRNAs associated with GBC risk in Europeans. Furthermore, the first GBC risk prediction model was drafted for Chilean patients.

WP 6
All Latin American PhD students have been accepted at the Medical Faculty of Heidelberg University. One Latin American PhD student has moved to the coordinating center in Heidelberg to start his second phase of the PhD.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The direct results (scientific publications, PhD training, advanced courses, … ) of ongoing project activities (patient recruitment, molecular characterization, 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 want 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 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. The article was translated into Spanish language and published in the Revista Médica de Chile.

b. Capacity building and research targeting. EULAT Eradicate GBC positively influences the development and enhancement of research skills in individuals and teams, including study nurses, clinicians, research technicians and PhD students, Masters students and postdoctoral fellows, junior researchers and 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 (GIST) to improve the transfer and communication of the project’s outputs. A podcast with GIST is available on Podcasts GIST Chile.
The EULAT Eradicate GBC dissemination videos are available in Native American languages (Aymara, Quechua, Mapudungun) and our manuscripts with ethnic aspects are reviewed by Mapuche culture experts prior to submission.

EULAT Eradicate GBC Logo