Is Pancreatic Cancer Hereditary?

Cancer of the pancreas is a genetic disease, which means that it is caused by changes (mutations) in DNA. These changes can be inherited (we are born with them) or they can be acquired (they develop after we are born). The inherited changes explain why cancer of the pancreas runs in some families, and the acquired changes can be the result of either bad luck during cell replication or by exposure to carcinogens (cancer causing chemicals) such as those found in cigarette smoke.

Hereditary pancreatic cancer is a current area of research at Johns Hopkins, and if you or a family member has been diagnosed with a pancreatic tumor, you can benefit our research study by joining our registry. It has been estimated that ten percent of pancreatic cancers are hereditary. Many of these occur as part of rare medical syndromes. These include: It has been estimated that >30% of pancreatic cancer is hereditary. About 5-10% of pancreatic cancers occur due to high-risk disease-causing changes in hereditary cancer genes. These genes include BRCA2, BRCA1, ATM, PALB2, CDKN2A, and DNA mismatch repair genes.

Familial pancreatic cancer
It has now become clear that pancreas cancer by itself (not part of a known syndrome) runs in some families, only about 20% of families with a clustering of pancreatic cancer have an identifiable mutation in a known gene. For example, relatives of patients with pancreas cancer have an increased risk for developing pancreas cancer themselves, and the National Familial Pancreas Tumor Registry (NFPTR) now contains over 1,953 families in which two or more family members have had pancreas cancer.

Scientists at Johns Hopkins are working diligently to discover the reasons why pancreas cancer runs in these families. To learn more about familial pancreas cancer please contact us at

How to Join NFPTR


Established Pancreatic Cancer Susceptibility Genes

Familial Breast and/or Ovarian Cancer Gene (BRCA1 and BRCA2)
BRCA1 and BRCA2 (breast cancer genes 1 and 2) are most commonly known for their association with hereditary breast and/or ovarian cancer (HBOC). Pancreatic cancer is the 3rd most common cancer associated with these genes. The BRCA2 gene produces tumor suppressor proteins. This is the second familial breast cancer gene identified. It was discovered because of a remarkable advance made by the Hopkins team studying pancreas cancer.

It is estimated that about 2-8% of pancreatic cancer patients, regardless of family history, have a mutation in the BRCA2 gene. This number is around 6-16% for patients with a close family relative with pancreatic cancer, and up to 17% in families with 3 or more pancreatic cancers. The risk of developing pancreatic cancer is about ~2-6 fold among individuals who have a BRCA2 gene mutation and about ~2-5 fold in BRCA1 carriers, compared to the general population.

PALB2 gene
PALB2 stands for "partner and localizer of BRCA2". This gene contains the information to make the PALB2 protein. This protein works together with theBRCA2 protein to repair damaged DNA. The PALB2 protein is believed to stabilize the BRCA2 protein, allowing the BRCA2 protein to repair damaged DNA. Through the study of families in the NFPTR, we discovered that about 1-4% of patients with familial pancreatic cancer have inherited mutations in the PALB2 gene. At this time, the lifetime risk of pancreatic cancer among individuals who inherit a PALB2 gene mutation is unclear, but studies are underway to better understand the risk of pancreatic cancer associated with mutations in this gene. Mutations in the PALB2 gene have also been associated with an increased risk of breast cancer.

ATM gene
ATM is a gene that has an important role coordinating DNA damage repair. ATM is also involved in preventing tumor development. The NFPTR team at Johns Hopkins led a collaborative study with the Pancreatic Cancer Genetic Epidemiology (PACGENE) consortium, which identified that some inherited changes in the ATM gene increased risk of pancreatic cancer. These diseasing–causing changes in ATM are found in 1-5% of patients with pancreatic cancer.

Peutz-Jeghers Syndrome (STK11 gene)
This is a very rare hereditary syndrome, caused by hereditary mutations in the STK11 gene, in which affected family members develop polyps in their small intestines and pigmented spots on their lips. These polyps are masses of tissue that protrude from the normal surface of the intestine. Patients with Peutz-Jeghers syndrome (PJS) are at a very high risk of developing cancer during their lifetimes, particularly gastrointestinal and gynecological cancers. Studies with Johns Hopkins GI SPORE demonstrated that patients with Peutz-Jeghers syndrome have a 76-140 fold increased risk of developing pancreas cancer compared to the general population.

Hereditary Melanoma CDKN2A/p16 gene
Inherited changes in the CDKN2A/p16 gene, a tumor suppressor gene, are responsible for familial melanoma. These patients also have an increased risk of developing pancreas cancer; approximately a 15-80 fold increased risk in carriers of CDKN2A/p16, compared to the general population.

Lynch Syndrome (mismatch repair genes)
Lynch syndrome or Hereditary non-polyposis colorectal cancer strikes as many as 1 in 200 individuals in the US and it is characterized by the inherited predisposition to develop colon cancer, endometrial (uterine) cancer, stomach cancer, and ovarian cancer. Inactivating mutations of DNA mismatch repair genes: MLH1, MSH2, MSH6, and PMS2 cause Lynch Syndrome. Patients with Lynch Syndrome may also have an increased risk of developing pancreas cancer. Indeed, the DNA finding typical of Lynch Syndrome, called microsatellite instability has recently been reported in a small (> 4%) fraction of pancreas cancers.

Hereditary Pancreatitis.
The genes PRSS1 and SPINK1 are both associated with hereditary pancreatitis. Individuals with hereditary pancreatitis develop severe, chronic inflammation of the pancreas at a young age, typically in their teenage years. Individuals with hereditary pancreatitis are at a very high-risk of developing pancreatic cancer, about 40% in their lifetime. Mutations in these genes are extremely rare and account for < ½ % of familial pancreatic cancer.

Since the NFTPR is a research study, it is not a surrogate for genetic testing and clinical risk assessment. However, our research had provided the scientific basis of current clinical risk assessment and management. Including the discovery that ATM and PALB2 are high-risk pancreatic cancer genes. Your participation greatly aids our research team in their efforts, and we hope our findings will eventually help families like your own. We feel it is very important to keep participants informed of our research findings, including overall study results, and try to provide information on how to access new clinical tests when they become available.

Clinical tests and panel testing are now available for several gene mutations known to increase the risk of pancreatic cancer, such as those mentioned above. Although these tests are available, they may not be right for everyone. In deciding whether or not you want to have a gene test performed, you should speak with a trained genetic counselor or your health care provider so that you are fully informed of the issues.

Additional Risk Factors

In addition to inherited risk factors, additional lifestyle or environmental factors are also believed to influence a person's risk of developing pancreatic cancer.

  • Cigarette smoking is the most preventable cause of pancreatic cancer. Cigarette smoking accounts for 25-30% of pancreatic cancers. Smoking cigarettes doubles the risk of pancreatic cancer, regardless of race. Cigarette smoking is the most preventable cause of pancreatic cancer.
  • Diet: The risk of pancreatic cancer is elevated in diets high in fat and calories. Processed meat high in nitrates, such as bacon and bologna, also increase the risk. The human body may process nitrates into cancer causing chemicals, called carcinogens.
  • Body Mass Index: The risk of pancreatic cancer increases with body mass.
  • Diabetes Mellitus: There are two types of diabetes, Type I and Type II. Type I diabetes has not been linked to pancreatic cancer. However, Type II diabetes, which tends to occur in adults, has been shown to double the risk of pancreatic cancer. Type II diabetes is associated with obesity and lack of exercise. Type II diabetes doubles the risk of pancreatic cancer. Diabetes can sometimes be caused by pancreatic cancer.
  • Pancreatitis: Pancreatitis is an inflammatory disease of the pancreas. Pancreatitis may either be acute (sudden and severe) or chronic (long-standing). Individuals that have had repeated attacks of acute pancreatitis can develop chronic pancreatitis. The risk of pancreatic cancer is elevated in all patients with pancreatitis.