A study conducted by scientists from Inserm, CNRS, Lille University Hospital, University of Lille, Institut Pasteur de Lille, published in the journal
Diabetes, reveals how type 2 diabetes can provoke epigenetic changes leading to pancreatic cancer. Led by Dr. Amna Khamis and Prof. Froguel from the University of Lille, this research offers new insights for preventing and treating one of the most aggressive cancers.
Patients with type 2 diabetes have a higher risk than non-diabetics of developing pancreatic cancer. This is one of the deadliest cancers because it is generally diagnosed too late. It is crucial to understand the early events related to diabetes that promote the development of this cancer in order to better prevent and fight it.
In this study, the researchers analyzed DNA from pancreatic tissue samples of 141 donors. They discovered that diabetes causes an epigenetic change, meaning a biochemical modification of a gene that alters its activity level without changing the DNA structure. In this case, it involves hypermethylation of the PNLIPRP gene, a modification that reduces its activity.
This gene is involved in lipid metabolism within the exocrine pancreas, the part of the pancreas responsible for secreting digestive enzymes. The results show that this modification of the PNLIPRP1 gene is linked to hyperglycemia and the consequent hyperlipidemia of type 2 diabetes, and that it leads to cellular changes in the exocrine pancreas typical of precancerous states.
Additionally, the study reveals that rare or frequent mutations in the PNLIPRP1 gene are associated with abnormalities in glycemic control, demonstrating for the first time the role of the exocrine pancreas, not just the endocrine pancreas (the part of the pancreas that secretes insulin), in the onset of type 2 diabetes. Overall, the PNLIPRP1 gene and lipid metabolism appear to play a key role in a vicious cycle linking diabetes, pancreatic cancer, and the exocrine pancreas.
The researchers suggest that the use of statins, drugs commonly used to lower cholesterol, could interrupt this process at the cellular level and thus protect patients against pancreatic cancer.
Type 2 diabetes affects approximately 4 million people in France and 537 million globally, and this number is continually rising. Diabetic patients are at an increased risk of developing pancreatic cancer, which remains one of the most aggressive with around 14,000 new cases per year in France and 460,000 worldwide. This cancer is often diagnosed late, making prevention crucial.