Back in the 1990s, little was known about the genetic underpinnings of pancreatic cancer.
Fast forward about 30 years, and today scientists know inherited genetics accounts for roughly 20-30 percent of pancreatic cancers. But only about 7-10 percent of pancreatic cancer patients will have an inheritable germline mutation, such as BRCA, found in testing. Another 5-10 percent or so will have a family history of pancreatic cancer, but not a known mutation.
Because of this increased knowledge, doctors now also know that some patients with germline mutations tend to have better outcomes. For example, some mutations may affect genes required for DNA repair, increasing their sensitivity to certain drugs—such as PARP inhibitors or platinum-based therapies such as oxaliplatin—used in patients with BRCA mutations. So regimens containing these drugs could become first-line treatment for those patients.
The National Familial Pancreatic Tumor Registry Has Contributed Much to Research
Although researchers across the globe are working diligently to better understand the basic biology of pancreatic cancer, much of the understanding gained over the last several decades can be attributed to the work of the National Familial Pancreatic Tumor Registry (NFPTR), an ongoing research registry started at Johns Hopkins Medicine (Baltimore, Maryland) in 1994. The multi-disciplinary group of experts has published more than 100 peer-reviewed studies, and the data gleaned from those studies not only helps inform the work of other researchers but has also shown that individuals with a family history of pancreatic cancer are at increased risk themselves.
The NFPTR’s work has also uncovered important pancreatic cancer susceptibility genes and aided in the development of tools to identify individuals at high risk for the development of the disease. “Our data shows that pancreas cancer risk is really very strongly dependent on family history, and that family history includes the degree of relationships, such as first-degree relatives like a parent or sibling versus a second-degree relative like an aunt, as well as the age those relatives developed pancreas cancer,” explains Alison Klein, Ph.D., M.H.S., director of the NFPTR. “Having relatives with the disease, no matter what degree, does not mean you’re going to develop pancreas cancer. But it does mean your risk is much higher than other people. So knowing risk is clearly important. It’s a terrible disease, so we want to catch it early in those who are deemed high-risk.”