Gene mutation can increase women's risk of pancreatic cancer

A recent study published in the journal Cellular and Molecular Gastroenterology and Hepatology has identified a gene mutation called ATRX as a potential driver of increased pancreatic cancer risk — but only in women. This marks the first time researchers have discovered a sex-specific genetic risk factor for pancreatic cancer, a disease that is notoriously difficult to detect early and remains one of the most lethal cancer types worldwide.

Using a preclinical model, the research team deleted the ATRX gene to study its effects on the adult pancreas. In women, the deletion increased susceptibility to pancreatitis-related pancreatic damage and accelerated the progression of pancreatic cancer. Strikingly, the same mutation had the opposite effect in men — it did not increase the risk of pancreatic damage and actually appeared to slow cancer progression. These findings suggest that the ATRX gene plays a fundamentally different biological role depending on sex, a distinction that has rarely been explored in cancer genetics research.

To validate these results, the team cross-referenced their findings with human samples from the International Cancer Genome Alliance database, which includes whole-genome sequence analysis of 729 patients. They found that 19% of patients carried mutations along the ATRX gene — and of those, 70% were female. Mutations predicted to disrupt ATRX protein function occurred almost exclusively in women, strongly supporting the preclinical findings.

Pancreatic cancer is frequently diagnosed at an advanced stage, leaving patients with very limited treatment options. As Dr. Chris Pin, Lawson scientist and associate professor, noted, the average lifespan following diagnosis is less than six months. Pancreatitis — inflammation of the pancreas — is one of the most significant known risk factors for developing the disease, yet no sex-specific genetic screening tools currently exist to identify which patients are most at risk.

This research changes that picture. Women with pancreatitis who carry ATRX mutations may one day be identified as a distinct high-risk group, enabling earlier monitoring and intervention before cancer develops. In a planned follow-up study, Dr. Pin will collaborate with French researchers to study patient tumor samples in a new preclinical model, with the goal of better understanding the exact mechanism by which ATRX mutations act as a sex-specific risk factor — and ultimately developing more targeted diagnostic and treatment strategies for women carrying this mutation.