What is familial pancreatic cancer? What you need to know

What is familial pancreatic cancer?

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

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

A family is considered to have FPC if first-degree relatives such as parents, children or siblings have a history of at least 2 cases of pancreatic cancer, or if at least 3 family members have pancreatic cancer. Healthy individuals from an FPC family are likely to have an increased lifetime risk of developing pancreatic cancer.

What causes familial pancreatic cancer?

Individuals in FPC families should consider whether their family’s pancreatic cancers could be caused by a specific germline (inherited) genetic mutation and consider a genetic test to determine this. A germline mutation is a genetic mutation present in every cell of a person’s body from birth.

Inherited mutations in the following genes may be found in FPC families:

BRCA1, BRCA2, PALB2, CDKN2A, ATM and 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 in Peutz-Jeghers syndrome) may also increase pancreatic cancer risk.

Individuals carrying germline genetic mutations in these genes are at increased risk of pancreatic cancer as well as other cancer types. Genetic tests are available for these genes, but your decision to undergo genetic testing should be carefully discussed with a medical professional with expertise in this field.

Genetic testing is still evolving, and a mutation identified through genetic testing can be found in only 10% to 20% of FPC families.

The fact that most FPC families currently have normal genetic test results suggests that the genes responsible for the FPC family have not yet been discovered. Researchers therefore continue to look for other specific genes that may be linked to FPC. Because most FPC families have normal genetic test results, individuals from FPC families remain at increased risk of pancreatic cancer even if their genetic test results are normal.

How is FPC passed on to later generations?

Normally, each cell contains 2 copies of a gene, one inherited from the mother and one from the father. Although the specific genes causing FPC are not fully known, researchers believe that FPC follows an autosomal dominant inheritance pattern, and a mutation in only one copy of a gene is sufficient for it to occur. This means that a parent with a gene mutation can pass a copy of either the normal gene or the mutated gene to their child. Therefore, a child with a parent carrying the mutation has a 50% chance of inheriting it. The brother, sister or parent of a person with the mutation also has a 50% chance of carrying the same mutation. However, if the parents test negative for the mutation (no mutation is found in their test results), the risk to siblings is significantly reduced, although their risk may still be higher than average.

Options are available for people with an inherited cancer syndrome who want to have children. Preimplantation genetic diagnosis (PGT), performed in conjunction with in vitro fertilization (IVF), is a medical procedure that may allow people to have a child without passing on a specific gene mutation. The woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size (approximately 8 cells), 1 cell is removed and tested for the inherited condition in question. Parents can then choose to transfer embryos without the mutation into the woman’s uterus. PGT has been used for more than twenty years to prevent various inherited cancer predisposition syndromes. However, it is a complex procedure requiring consideration of financial, physical and emotional factors before starting PGT.

How common is FPC?

This year, an estimated 57,600 adults (30,400 men and 27,200 women) in the United States are expected to be diagnosed with pancreatic cancer. According to the 2020 Turkey Cancer Statistics, 8,392 people in Turkey were diagnosed with pancreatic cancer in 1 year. Approximately 10% of these cases are thought to result from FPC.

How is FPC diagnosed?

FPC is a term used to describe families with a concentration of pancreatic cancer diagnoses. There is currently no specific test for FPC. Families are considered to have FPC in the following circumstances:

• The family has two or more first-degree relatives, such as parents, children or siblings, diagnosed with pancreatic cancer, or
• The family has 3 or more close relatives on the maternal or paternal side diagnosed with pancreatic cancer.

Talk to your doctor if you have symptoms of pancreatic cancer. You will have a physical examination and be asked about your medical history. Your doctor will also recommend specific tests to help find pancreatic cancer.

What are the estimated cancer risks associated with FPC?

For an average individual with no family history of pancreatic cancer, the lifetime risk of pancreatic cancer is approximately 1%. Individuals with a family history of pancreatic cancer are at risk of developing pancreatic cancer during their lifetime. This risk is probably higher for individuals from an FPC family. The following cancer risk estimates are generalized and should be interpreted cautiously because the actual risk may differ for each individual:

• Individuals from FPC families who have a parent, sibling or child with pancreatic cancer are estimated to have a pancreatic cancer risk 3 to 5 times higher than the general population.
• Individuals from an FPC family who have 2 first-degree relatives with pancreatic cancer are estimated to have a lifetime pancreatic cancer risk 5 to 7 times higher than the general population.
• Individuals from FPC families with 3 or more first-degree relatives with pancreatic cancer are estimated to have a lifetime pancreatic cancer risk 30 times higher than the general population.

People carrying germline mutations in genes known to be linked to pancreatic cancer risk (BRCA1, BRCA2, PALB2, CDKN2A, ATM, TP53, STK11, MLH1, MSH2, MSH6, PMS2 and EPCAM) are also at increased risk of several cancers, including pancreatic cancer. For individuals with a mutation in one of these genes, pancreatic cancer risk may be particularly high if there is a family history of pancreatic cancer. Recent research has found that 4% to 10% of individuals with pancreatic cancer have a mutation in one of these genes. Ashkenazi Jewish individuals with pancreatic cancer are more likely to carry one of these genetic mutations.

Some national guidelines recommend genetic testing for anyone diagnosed with pancreatic cancer, regardless of their family cancer history or age at diagnosis.

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

What are the screening / early detection options for FPC?

Whether pancreatic cancer screening is effective is not known, and there is currently no routine pancreatic cancer screening recommended for the general population. Researchers continue to investigate whom to screen, which tests to use and how often to use them.

Given that individuals from FPC families or those with germline genetic mutations in BRCA1, BRCA2, PALB2, CDKN2A, ATM, MLH1, MSH2, MSH6, PMS2, STK11 and EPCAM are at increased risk of pancreatic cancer, screening these high-risk individuals for pancreatic cancer is particularly important. Because every person is different, it is important to talk to your doctor about the following screening options.

Current guidelines state that healthy individuals from FPC families should start pancreatic cancer screening at age 50 or 10 years before the earliest pancreatic cancer diagnosis in the family, if at least one of the relatives with pancreatic cancer is a first-degree relative (for example, if someone in the family was diagnosed with pancreatic cancer at age 40, your screening should start at age 30). The guidelines also recommend screening individuals with germline mutations in the genes listed above starting at age 50 or 10 years before the earliest pancreatic cancer diagnosis in the family if there is a family history of pancreatic cancer. Some experts recommend screening those with the STK11 gene (which causes Peutz-Jeghers syndrome) or the CDKN2A gene (which causes familial atypical multiple mole melanoma syndrome), regardless of family history. Patients with Peutz-Jeghers syndrome are advised to start screening at ages 30 to 35, while those with familial atypical multiple mole melanoma syndrome are advised to start at age 40. The most commonly used screening tests are as follows:

• Magnetic resonance imaging (MRI) – 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 descends into the small bowel to take an image of the pancreas.

Screening options are likely to change over time as new technologies are developed and more is learned about FPC. You can talk to your doctor about the screening tests that are right for you.

Questions to ask your doctor

If you are concerned about your risk of developing pancreatic cancer, talk to your healthcare team. It may be helpful to bring someone to your appointments to take notes. You can ask your healthcare team the following questions:

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

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

• Does my family history increase my risk of pancreatic cancer?
• Do I have options for cancer screening? If so, what are they?
• Should I see a genetic counselor or another genetics specialist?
• Should I consider genetic testing?

*