The finding, which is published in the journal ‘GUT’, could help identify groups at risk of pancreatic cancer, that is, individuals on whom to focus prevention and early detection efforts and understand how to do it. Pancreatic cancer is on the rise, and within a decade, it could become the second leading cause of cancer death globally. One reason is that it is not known how to detect it early, so it is often diagnosed when the disease is already in advanced stages. Oncology aims to "understand what precedes pancreatic cancer, to try to prevent it or diagnose it at very early stages," says Francisco X. Real, head of the Epithelial Carcinogenesis Group at the Spanish National Cancer Research Center (CNIO).
Together with his team, Real presents a finding that could help identify groups at risk of pancreatic cancer, that is, individuals on whom to focus prevention and early detection efforts and understand how to do it. The study is published in the journal GUT. The variant that increases the risk of the tumor is present in 17% of the population, and the risk increase it confers by itself is not high. But the increase could be significant if the mutation is combined with other factors, such as smoking, obesity, alcohol consumption, or diabetes, which are known to promote pancreatic cancer (like the majority of tumors, pancreatic cancer is caused by a combination of environmental and hereditary factors).
"When this genetic variant appears along with other factors, such as diabetes or pancreatitis, or with other genetic variants, the risk could increase. This allows us to identify a population at high risk on which prevention strategies could be developed," explains Real. In pancreatic cancer, there are still no tests specific, sensitive, and non-invasive enough to screen the population. Due to its location in the body, it is difficult to access the pancreas. Hence the importance of identifying high-risk groups.
This mutation in the CTRB2 gene had already been identified in previous work by the CNIO group and other collaborators. The new study, with researchers Cristina Bodas and Irene Felipe as first authors, confirms its causal role.
ANIMAL MODEL RESEARCH
The group created an animal model in mice with the same mutation present in humans and found that it dramatically alters fundamental aspects of how pancreatic cells function. "Damage to the pancreas of animals with the mutation could be seen, using genomic techniques, in very young mice," says Real. The authors, in collaboration with the CNIO’s Genetic and Molecular Epidemiology Group, led by Núria Malats, then confirmed that the same phenomenon occurred in humans with the mutation: alterations in the pancreas before cancer developed.
The next steps for the CNIO group focus on investigating how the new mutation in the CTRB2 gene collaborates with other factors associated with pancreatic cancer. Not only with pathologies like diabetes or pancreatitis mentioned earlier, but also with mutations in the KRAS gene, which is known to be mutated in over 90% of cases of pancreatic ductal adenocarcinoma (the most common subtype of pancreatic cancer). The goal is to identify "a population at much higher risk of developing the disease, for which we can propose preventive strategies," emphasizes Real.
