Researchers Identify a Gene Mutation that Increases the Risk of Pancreatic Cancer

Researchers from the Dana-Farber Cancer Institute have identified a rare, inherited gene mutation that significantly increases the risk of developing pancreatic cancer. The findings were published in journal Nature Genetics.

Approximately 10 percent of pancreatic cancers possess a familial pattern, however, in most cases the genetic flaw is unknown.  One genetic mutation that cause a predisposition to pancreatic cancer occurs in the gene called BRCA2, and this gene is also known to cause some forms of breast and ovarian cancer. The researchers found a mutation in the gene RABL3 that similarly augments the odds of developing cancer. the likelihood that cancer will develop during the person’s lifetime. This discovery could lead to enhanced screening to detect pancreatic cancer in before it metastasizes. “There is evidence that catching pancreatic cancer through screening of high-risk individuals may improve outcomes,” said Sahar Nissim, MD, PhD, a cancer geneticist and gastroenterologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, and first author of the study in a press release. In addition, the author noted, that relatives could choose to be tested to discern if they too carry the mutation.

All in The Family

The researchers pinpointed the RABL3 mutation after studying a family that comprised five family members with pancreatic cancer and multiple other members with other forms of cancer. This pattern was indicative of predisposition triggered by an inherited mutation. of an inherited mutation. In their analysis, the researchers sequenced the DNA of two family members – one who had developed pancreatic cancer at the age of 48, and another, the first patient’s paternal uncle, who had developed pancreatic cancer at the age of 80. Subsequently, the RABL3 mutation was discovered in several other family members with cancer, and even in one without the disease.

Because confirming a new genetic mutation can take years of testing a litany of families around the world, to expedite the process the researchers used the zebrafish model. By repeating their findings in a large zebrafish population, they were able to perform rapid epidemiological studies that appraised the impact of the RABL3 mutation. They found that like humans, zebrafish carrying the RABL3 mutation exhibited notably higher rates of cancer.

“This work highlights the power of studying and understanding rare family syndromes: from just one family, we have uncovered broadly important insights into pancreatic cancer and how we may better prevent or treat it,” Dr. Nissim continued. “While testing for this specific genetic mutation is not available on current commercial genetic testing panels, we anticipate that the commercial tests will incorporate mutations in this gene in future panels.”

Dr. Nissim added that he and his colleagues “anticipate that testing for this genetic mutation will be recommended in any individual with a strong family history of pancreatic cancer.”