Pancreatic cancer occurs when cells in the pancreas grow abnormally. While most are not, up to 10% of cases of pancreatic cancer are inherited. Hereditary pancreatic cancer (HPC) occurs when a person has a genetic change (mutation) that causes their skin cells to be more likely to become cancerous. The mutation can be passed through generations in a family. Women and men with HPC have a higher risk of developing pancreatic cancer, and sometimes other cancers or health problems, as well.

Cancer-risk genes are genes that can impact whether a cell will begin to grow uncontrollably into cancer. We have two copies of every gene, one from our mother and the other from our father. Hereditary pancreatic cancer is most commonly inherited in an autosomal dominant way. For dominant conditions, having only one copy of a gene mutation is enough to cause symptoms. In the case of dominant HPC, having one mutation leads to an increased risk for cancer. If a person has a mutation in one gene for dominant HPC, there is a 50% risk that each of their children will inherit this mutation. Siblings, parents, and potentially other relatives could also have the mutation. Importantly, not everyone who has a mutation in a cancer-risk gene will develop cancer, but their chances are higher. While rare, it is possible for a person to have a mutation for a dominant condition that is absent from both of their parents. In this situation, the mutation arose early before they were conceived or born. This is called de novo inheritance. Even after de novo inheritance, if a person has a mutation in one dominant gene for hereditary pancreatic cancer, each of their children will have a 50% risk to inherit the mutation. In rare cases, HPC can be inherited in an autosomal recessive way. For recessive conditions, both copies of a person’s gene must have a mutation before they will have an increased risk for cancer. Typically, an individual with a recessive condition will have inherited one mutation from their mom and one from their dad. Because the mom and dad have another copy of the gene without the mutation, they will usually not show symptoms. For these parents, there is a 25% risk with each pregnancy that the child will inherit both the mom’s and the dad’s mutations, and therefore, will have the recessive condition.

Patients identified with hereditary pancreatic cancer can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Information obtained from candidate gene testing may potentially be helpful in guiding clinical management in the future. Also, if an inherited susceptibility is found, your patient’s family members can be tested to help define their risk. If a pathogenic variant is identified in your patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also be at increased risk. In some cases, screening should begin in childhood.

Hereditary pancreatic cancer syndromes are conditions that impact other areas of an individual’s body in addition to increasing their risk for pancreatic cancer. A syndrome can be inherited in a dominant, de novo, or recessive manner. Some examples of hereditary pancreatic cancer syndromes are listed below.

Peutz-Jegher Syndrome (PJS)

PJS is associated with a combination of unusual pigmentation on the face, inside the mouth, and on the fingers in childhood, gastrointestinal polyps (especially in the small intestine), and an increased risk for cancer. For pancreatic cancer, the risk is estimated at between 11% and 36%. Individuals with PJS have a mutation in the STK11 gene. The condition is dominant, so the risk to pass on the mutation is 50% with each pregnancy.

Familial Atypical Multiple Mole Melanoma (FAMMM)

 Individuals with FAMMM have a higher risk for pancreatic cancer, can have many atypical moles, and are more likely to develop melanoma. FAMMM is caused by mutations in the CDKNA gene, which is inherited in a dominant way.

Lynch syndrome

Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is caused by a mutation in of five genes whose jobs are to repair the DNA damage that normally occurs as cells grow and divide. The condition shows dominant inheritance. People with Lynch syndrome have up to a 3.7% risk for pancreatic cancer and an 80% risk to develop colon cancer by age 70 years. They are also at an increased risk for many other types of cancers, such as endometrial, gastric, and prostate.


Hereditary Breast and Ovarian Cancer (HBOC)

Two genes, named BRCA1 and BRCA2, are common causes of dominant hereditary breast cancer. Mutations in these two genes are also associated with a significant risk for breast cancer, as well as ovarian and prostate cancer. A mutation in BRCA2 also confers a higher risk for breast cancer in men, and melanoma for both men and women. Individuals with BRCA2 mutations have approximately 17-19% risk for pancreatic cancer.

A person with an average risk of pancreatic cancer has about a 1% chance of developing the disease. Generally, most pancreatic cancers (about 90%) are considered sporadic. Also called somatic mutations, this means the genetic changes develop by chance after a person is born. There is no risk of passing these genetic changes on to one’s children.

Family history. Pancreatic cancer may run in the family and/or may be linked with genetic conditions that increase the risk of other types of cancer. This is called familial pancreatic cancer. You and your family may be at risk if 2 or more first-degree relatives or at least 3 members of the family have been diagnosed with pancreatic cancer. First-degree relatives include parents, children, and siblings. ASCO encourages people diagnosed with pancreatic adenocarcinoma to talk with their doctor about their family history of cancer. Even without a strong family history, people diagnosed with pancreatic adenocarcinoma may want to consider genetic testing for hereditary pancreatic cancer

Rare inherited conditions. Members of families with certain uncommon inherited conditions also have a significantly increased risk of pancreatic cancer, as well as other types of cancer.

Diabetes. Many studies have indicated that diabetes, especially when a person has had it for many years, increases the risk of developing pancreatic cancer. In addition, suddenly developing diabetes later in adulthood can be an early symptom of pancreatic cancer.

Obesity and diet. Regularly eating foods high in fat is a risk factor for pancreatic cancer. 

Smoking. People who smoke are 2 to 3 times more likely to develop pancreatic cancer than those who don’t.

Age. The risk of developing pancreatic cancer increases with age. Most people who develop pancreatic cancer are older than 45. In fact, 90% are older than 55 and 70% are older than 65. However, adults of any age can be diagnosed with pancreatic cancer.


 A positive result means that a genetic mutation causing an increased risk for pancreatic cancer was identified. Your risk for other cancers or health conditions may also be increased, depending on the gene involved. Your doctor can use this information to customize your care, which could include increased screening, preventative surgery, medication, and other steps. A positive result is also important for your family. Your parents, siblings, and children could have as high as a 50% chance to also have the mutation. As a result, sharing your genetic testing results with your relatives is important for their health.


 A negative result indicates that a genetic mutation was not identified. A negative result may indicate that there is not a cancer-risk gene mutation in you or your family. However, it can also mean that the gene increasing risk in you or your family was not included on the ordered test, or even that it may not be currently known by scientists. Your doctor can use a negative result to continue your treatment and screening based on your clinical and family history, or they may consider another type of genetic testing.


The third possible test result is called a Variant of Uncertain Clinical Significance. A gene variant is a genetic difference that could be disease-causing (mutation) or could be a normal finding (benign). More research is needed to determine whether the variant is important or not, and it should be treated as a negative result until more information is available.