A recent study published in the journal Cellular and Molecular Gastroenterology and Hepatology showed that a gene mutation called ATRX may lead to an increased risk of pancreatitis and pancreatic cancer in women. This study marks the first discovery of sex-specific genetic risk factors for pancreatic cancer.
The team used a preclinical model to examine the effect of ATRX mutations on the adult pancreas. They deleted the ATRX gene and then studied its effect on pancreatic cancer susceptibility. The team found that the deletion of the ATRX gene in women increased the susceptibility to pancreatitis-related pancreatic damage and accelerated the progression of pancreatic cancer. In men, ATRX mutations do not increase the risk of pancreatic damage, and actually slow the progression of pancreatic cancer.
The team ’s preclinical results were compared with human samples from the International Cancer Genome Alliance database, which includes whole-genome sequence analysis of 729 patients. The research team found that 19% of patients carry mutations in the length of the ATRX gene, including non-coding regions, of which 70% are female. Although most mutations do not seem to disrupt the ATRX protein sequence, mutations predicted to affect ATRX function occur almost exclusively in women.
Lawson scientist and associate professor Dr. Chris Pin said, “Pancreatic cancer is a very devastating disease that is often diagnosed at an advanced stage. Patients usually do not respond to existing therapies, and the average lifespan of patients is after diagnosis Less than 6 months. “Pancreatitis is a disease characterized by inflammation of the pancreas and one of the most important risk factors for developing pancreatic cancer. Although further research is needed, women with pancreatitis may one day be identified as a high-risk group, and this gene mutation should be screened.
In a follow-up study, Dr. Pin will work with French researchers to study patient tumor samples in a new preclinical model. Their goal is to better understand the mechanism of ATRX mutations as a gender-specific risk factor. In order to develop better diagnosis and treatment methods for women carrying this mutation.
