i3S researchers take an important step in the diagnosis of Hereditary Gastric Cancer – Jornal Universitário do Porto

In 2024, a consortium of specialists will take place in Porto where the mutations identified in the publication will be approved “Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes”, from the journal “The Lancet: Oncology”. The objective is to include them in the treatment of the disease.

The article referred to is about the collaboration between an international team, led by Carla Oliveira, principal investigator at i3S (Institute for Research and Innovation in Health), in Porto. In the study, European clinical data collected between 2018 and 2022 by 29 different laboratories, in ten European countries, from the ERN GENTURIS (European Reference Network on Tumor Risk Syndromes) were analyzed. Using data about the genetic information of the CDH1 gene (gene that encodes the E-Cadherin protein), and analysis of the phenotype (observable characteristics in individuals), we analyzed whether the mutations found translated into HDGC and evolved into tumors.

Three new pathogenic mutations were found and others that proved to have no influence on the appearance of the hereditary diffuse gastric cancer syndrome were discarded. From the results of this study, it was found that only mutations that result in the elimination of E-Cadherin protein production have an effect on the propensity to develop cancer. These new mutations described represent the opportunity for the application of new criteria in the diagnosis of this syndrome, the importance of early diagnosis of which is high.

Diffuse Hereditary Cancer Syndrome

Despite its name, HDGC syndrome often translates into gastric cancer in men but breast cancer in women at young ages, affecting more than 50,000 people a year worldwide. The research group at i3S has been studying the CDH1 gene and its relationship with this syndrome. With this study it was verified that “only the alterations that eliminate the production of Cadherin-E increase the risk of developing breast cancer and stomach cancer“, reveals the principal investigator Carla Oliveira in a statement.

This cancer does not yet have effective forms of treatment, and the best option, currently, is the removal of the breast or stomach, after the age of 18 and before the cancer manifests itself. Although drastic, this prophylactic treatment is currently the most effective treatment for people with this diagnosis. As it is a hereditary syndrome, researcher Carla Oliveira believes that the results of this study and the predictive measures will allow families to make more informed decisions for risk management in the whole family.

The study had the collaboration of members of ERN GENTURIS, as well as research groups from i3S «Population Genetics & Evolution» and «UnIGENe», «Ipatimup Diagnostics» and teams from Centro Hospitalar Universitário de São João (CHUSJ), Faculdade of Medicine of the University of Porto (FMUP), IPO-Porto, GenoMed, Center for Neurosciences and Cell Biology (CNC) of the University of Coimbra and Porto Comprehensive Cancer Center Raquel Seruca (PCCC).

With this discovery, the i3S group, through an example of international cooperation in Science, enabled the advancement in the diagnosis of Hereditary Gastric Cancer Syndrome. With the approval and start of application of these new diagnostic measures, another door is opened for the early treatment of several families that present these mutations.

Text by Maria Amaro. Reviewed by Maria Teresa Martins.