Familial pancreatic cancer

It is estimated that only 10-20% of families with familial pancreatic cancer (FPC) will have a mutation identified by genetic testing.^[1] This is because only some of the gene changes that increase pancreatic cancer risk can be tested for.^[2] In the absence of a known hereditary cancer syndrome or other inherited disorder associated with pancreatic cancer, a specific genetic cause for FPC has not yet been identified. In these cases, medical and family histories are relied upon to determine if family members may be at increased risk. When considering genetic testing, talking to someone with experience in hereditary cancers such as a genetic counselor, geneticist, or oncologist is strongly recommended.

Genetic testing for suspected familial pancreatic cancer may include analysis of the BRCA1, BRCA2, CDKN2A, PALB2, and ATM genes. Evaluation for Peutz-Jeghers syndrome, Lynch syndrome, or hereditary pancreatitis-associated genes may be considered if other personal and/or family history criteria are met for these conditions.^[3] Genetic counseling with a genetics professional or oncologist can help people determine whether genetic testing is appropriate, and which specific tests would be informative. The Pancreatic Cancer Action network provides useful information about genetic counseling for a family history of pancreatic cancer.

Guidelines for optimal screening strategies for people determined to be at risk for familial pancreatic cancer have been published by the International Cancer of the Pancreas Screening (CAPS) Consortium and the American College of Gastroenterology (ACG).

According to ACG, people should be considered at increased risk for familial pancreatic cancer if they:

• have a known genetic syndrome associated with pancreatic cancer or other gene mutations associated with an increased risk of pancreatic adenocarcinoma; or
• have two relatives with pancreatic adenocarcinoma, where one is a first-degree relative; or
• have three or more relatives with pancreatic cancer; or
• have a history of hereditary pancreatitis^[3]

The guidelines recommend that surveillance of those with a genetic predisposition should ideally be performed in experienced centers using a multidisciplinary approach and under research conditions. Tests used for surveillance may include endoscopic ultrasound and/or MRI of the pancreas annually starting at age 50, or 10 years younger than the earliest age of pancreatic cancer in the family.^[3] Doctors have been able to find early, treatable pancreatic cancers in some members of high-risk families with endoscopic ultrasound.^[2] People with Peutz-Jeghers syndrome may start surveillance earlier.^[3]

CA 19-9 is a tumor marker, a substance that is produced by cancer cells or other cells of the body in response to cancer (or other conditions). CA 19-9 and another tumor marker, carcinoembryonic antigen (CEA), are the ones most closely tied to pancreatic cancer.^[2] However, not every person with pancreatic cancer will have elevated levels of these markers; and even when levels are elevated, the cancer is often already advanced. Additionally, sometimes levels of these tumor markers are elevated when a person doesn’t have pancreatic cancer. For these reasons, blood tests such as CA 19-9 are not used as screening tests for pancreatic cancer (unless ordered when a person has symptoms that may be caused by pancreatic cancer).^[2][4] These blood tests may be used in people already diagnosed with pancreatic cancer, to help determine if treatment is working or if the cancer is progressing.^[2]

People at increased risk for familial pancreatic cancer who have questions about screening and testing are strongly encouraged to speak with an oncologist or a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.