Understanding a Family’s Risk for Pancreatic Cancer

With inherited genetic changes probably playing a role in many pancreatic cancers, researchers are keen to identify people at risk for the disease.

One huge step in helping to identify those individuals and families is through research geared toward developing ways doctors can more readily identify people who may be carriers of the genetic changes that put people at higher risk.

The first step: patient and family registries like the National Familial Pancreas Tumor Registry at Johns Hopkins (NFPTR.) The Johns Hopkins registry is a research-based endeavor that has been active for more than 20 years, explains Alison Klein, Ph.D., NFPTR director. “What we have been able to show is that pancreatic cancer does run or cluster in families and that there is likely to be a genetic cause to this clustering,” says Klein. “Pancreatic cancer, as we all know, has a very poor prognosis, so by studying families enrolled in our registry, we hope to find some answers as to how we can improve outcomes for patients like they have in other cancers.”

Currently, the registry has enrolled about 4,000 families — some which have more than one close relative who has been diagnosed with pancreatic cancer and others where only a single member of a family has the disease. All participants are vital to gaining a better understanding of the disease and developing not only early detection programs, but also personalized treatment plans.

Genetics Helps Find Answers

The Johns Hopkins registry has already been able to identify several familial pancreatic cancer susceptibility genes. And they were among the first to conduct early detection screening trials.

Other findings indicate that individuals who have a strong family history of pancreatic cancer have a nine-fold increase in the odds of developing the disease during their lifetimes.

“What we are doing is in one sense providing a frame for genetic counseling and screening,” says Klein, adding that the group developed a tool called PancPRO to help determine risk. “We know how genes behave, and coupled with information about a family — who has the disease, their age, family size, and causes of death — our model can provide a good estimate of an individual’s risk,” she adds.

Possible Genetic Culprits

Researchers know that inherited genes cause about 10 percent of pancreatic cancers, but inheriting these genes is not necessarily destiny, explains Klein. Essentially, if there is a 100 percent certainty that an individual carries a pancreatic cancer gene, that individual’s risk of being diagnosed with the disease during their lifetime is only about 25 percent.

Some of the genes that have been linked to familial pancreatic cancer may sound familiar, specifically BRCA2, the so-called breast cancer gene. Researchers at Johns Hopkins, and other teams, have shown that up to about 12 percent of familiar pancreatic cancers are linked to an inherited defect in this gene. The Johns Hopkins team is also studying patient-specific populations, like those of the Ashkenazi Jews and African-Americans.

Among African-Americans, who have high incidences of the disease and some of the poorest prognoses, early studies suggest that socioeconomic and environmental factors, such as cigarette smoking, may play a role. The population also has higher incidences of pancreatitis and diabetes, which have already been linked to the development of pancreatic cancer.

Ashkenazi Jewish families are also of vital importance to the team’s research efforts. “The incidence of pancreatic cancer in this population is also very high, and we don’t know yet if due to inheritance or the environment, for example, but by studying the family history, we may be able to find out,” says Klein.

Beyond institutions, genomics companies are also keeping registries to use data mining as a research tool. One example is Ambry Genetics’ Prospective Registry of MultiPlex Testing or PROMPT, which seeks to better understand changes in genes that have been tied to an increased risk of cancer. The intent is for this research to help determine the best ways to care for individuals with these changes. Patients don’t enlist in PROMPT like they do with NFTPR, but they become part of the registry once they have multi-gene or multiplex genetic testing done.

A Look to The Future

Going forward, the registry’s research work will continue to involve identification of those genes that place people at higher than average risk, and the development of ways to use those genetic discoveries and biomarkers to provide a means of early detection of pancreatic cancer. It’s a tall order, but one that Klein believes is ultimately possible.

“I think one of the most important things we can do as researchers do is to let the public know that progress is being made in pancreatic cancer,” she says. “We need to raise awareness of pancreatic cancer, and potentially have more patients and families involved in our research. The potential for diagnosing pancreatic cancer in its early stages, along with the tremendous work that’s being done on the treatment end, can be a very important difference as we try to beat this disease.”

To learn more, and to see if you and your family may be eligible to participate in this research, please visit the National Familial Pancreas Tumor Registry at Johns Hopkins.

Find more stories about promising science to combat pancreatic cancer at Let’s Win.