Familial Pancreatic Cancer

Approved by the Cancer.Net Editorial Board , 09/2021

What is Familial Pancreatic Cancer?

Familial pancreatic cancer (FPC) is a term to describe families with a high rate of pancreatic cancer .

The pancreas is a pear-shaped gland found in the abdomen between the stomach and spine. The gland makes enzymes that help the body digest food. It also makes hormones, such as insulin, that help control blood sugar. Ductal adenocarcinoma of the pancreas is the most common type of pancreatic cancer. It starts when healthy cells lining the pancreatic ducts change and grow out of control, forming a tumor.

Families are considered to have FPC if there are at least 2 members of the family with pancreatic cancer who are first-degree relatives, such as a parent, child, or siblings of one another, or if there are at least 3 members of the family who have pancreatic cancer. Healthy individuals who come from a family with FPC are likely to have an increased risk of developing pancreatic cancer in their lifetime.

What causes FPC?

Individuals from FPC families should consider genetic testing to see if there is a specific germline genetic mutation that may have caused the pancreatic cancers in their family. A germline mutation is a genetic mutation found in every cell of a person’s body from birth. Some genes linked to FPC families include BRCA1 , BRCA2 , PALB2 , CDKN2A , and ATM , and the genes linked to Lynch syndrome ( MLH1 , MSH2 , MSH6 , PMS2 , and EPCAM ). Germline mutations in genes that cause other rare inherited cancer syndromes ( TP53 mutations in Li-Fraumeni syndrome and STK11 mutations for Peutz-Jeghers syndrome ) also increase the risk of pancreatic cancer.  Individuals who carry germline genetic mutations in these genes are at an increased risk of pancreatic cancer as well as other types of cancers. Genetic testing for these genes is available, but your decision to have genetic testing should be discussed carefully with a medical professional with expertise in this area.

It is important to note that genetic testing is still evolving, and only 10% to 20% of families with FPC will have a mutation identified by genetic testing. Currently, most families with FPC will have normal genetic testing results, suggesting that the genes responsible for most FPC families have not yet been discovered. Researchers continue to search for other specific genes that may be linked to FPC. Since most FPC families will have normal genetic testing results, it is important to realize that individuals from FPC families are still at an increased risk of pancreatic cancer, even when genetic testing results are normal. Talk with a genetic counselor before you have any genetic testing .

How is FPC inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. Researchers think that FPC typically follows an autosomal dominant inheritance pattern, even though the specific genes that cause FPC are mostly unknown. In autosomal dominant inheritance, a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene. Or, that parent may pass along a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A sibling or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. A person's eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is FPC?

This year, an estimated 60,430 adults (31,950 men and 28,480 women) in the United States will be diagnosed with pancreatic cancer. About 10% of those cases are thought to be caused by FPC.

How is FPC diagnosed?

FPC is a term used to describe families with a clustering of pancreatic cancer diagnoses. At this time, there is no specific test for FPC. Families are considered to have FPC if there are:

  • 2 or more members of a family who are first-degree relatives, such as parents, children, or siblings, who have been diagnosed with pancreatic cancer, or

  • 3 or more close relatives from the same side of the family who have been diagnosed with pancreatic cancer.

If you have symptoms of pancreatic cancer, talk with your doctor. They will perform a physical exam and ask you about your medical history. Your doctor will also recommend specific tests to help find pancreatic cancer. Learn more about the symptoms and signs of pancreatic cancer .

What are the estimated cancer risks associated with FPC?

The lifetime risk of pancreatic cancer for the average individual without a family history of pancreatic cancer is approximately 1%. Individuals with a family history of pancreatic cancer are at an increased lifetime risk for developing pancreatic cancer. This risk is likely higher for individuals from a family with FPC. The following cancer risk estimates are generalized and should be interpreted with caution since the actual risk for each individual may be different:

  • Individuals from FPC families who have 1 first-degree relative, meaning a parent, sibling, or child, with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 3 to 5 times higher than the general population.

  • Individuals from FPC families who have 2 first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 5 to 7 times higher than the general population.
  • Individuals from FPC families who have 3 or more first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that may be up to 30 times higher than the general population.

Individuals who carry germline mutations in known genes linked to pancreatic cancer risk ( BRCA1 , BRCA2 , PALB2 , CDKN2A, ATM , TP53 , STK11 , MLH1 , MSH2 , MSH6 , PMS2 , and EPCAM ) are also at an increased risk of various cancers, including pancreatic cancer. For individuals with a mutation in 1 of these genes, the risk of pancreatic cancer may be particularly higher if there is also a history of pancreatic cancer in the family. Recent studies have found that 4% to 10% of individuals with pancreatic cancer will have a mutation in 1 of these genes. Individuals with pancreatic cancer who are of Ashkenazi Jewish ancestry are even more likely to carry 1 of these genetic mutations. Some national guidelines now recommend genetic testing for any person diagnosed with pancreatic cancer, regardless of their family history of cancer or age at diagnosis.

Tobacco use increases an individual’s lifetime risk of pancreatic cancer, regardless of their family history. Tobacco use may significantly increase the risk of pancreatic cancer for individuals from FPC families.

What are the screening options for FPC?

It is unknown if screening for pancreatic cancer is effective, and there is no routine screening for pancreatic cancer that is currently recommended for the general population. The medical community continues to research who to screen, which tests to use, and how often to use them.

Given that individuals from FPC families, or individuals with germline genetic mutations in BRCA1 , BRCA2 , PALB2 , CDKN2A, ATM , MLH1 , MSH2 , MSH6 , PMS2 , STK11, and EPCAM , are at increased risk for pancreatic cancer, there is much interest in researching pancreatic cancer screening for these high-risk individuals. It’s important to talk with your doctor about the screening options below, as each person is different.

Current guidelines recommend that healthy individuals from FPC families should consider pancreatic cancer screening beginning at age 50, or 10 years younger than the earliest pancreatic cancer diagnosis in the family, if at least 1 of the pancreatic cancers in their family was in a first-degree relative. Guidelines also recommend that individuals with germline mutations in the genes listed above should consider screening beginning at age 50, or 10 years younger than the earliest pancreatic cancer diagnosis in the family, if they have a family history of pancreatic cancer. Some experts have recommended that all individuals with germline mutations in STK11 (which causes Peutz-Jeghers syndrome) or CDKN2A (which causes familial atypical multiple mole melanoma [FAMMM] syndrome), have screening regardless of their family history, with Peutz-Jeghers syndrome patients being recommended to begin screening at age 30 to 35 and FAMMM syndrome patients being recommended to begin by age 40. The screening tests that are most commonly used include:

  • Magnetic resonance imaging (MRI) – An MRI uses magnetic fields to produce detailed images of the pancreas.
  • Endoscopic ultrasound (EUS) – A thin, lighted tube is passed through the patient's mouth and stomach. The tube goes down into the small intestine to take a picture of the pancreas.

Screening options are likely to change over time as new technologies are developed and more is learned about FPC. It’s important to talk with your doctor about screening tests that are right for you. Learn more about what to expect when having common tests, procedures, and scans .

Questions to ask the health care team

If you are concerned about your risk of developing pancreatic cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing pancreatic cancer?

  • What can I do to reduce my risk of cancer?

If you are concerned about your family history and think your family may have FPC, consider asking the following questions:

  • Does my family history increase my risk of pancreatic cancer?

  • If so, what are my options for cancer screening?

  • Should I meet with a genetic counselor or other genetics specialist?

  • Should I consider genetic testing ?

  • What are familial registries and surveillance programs?