FAQs

There are several factors that increase risk of pancreatic cancer, including cigarette smoking, increasing age, chronic pancreatitis, diabetes, heavy alcohol intake (>3 drinks per day) and obesity. In addition to these risk factors, individuals who have a family history of pancreatic cancer, as well as some other cancers (breast, ovarian, melanoma, colon), are at an increased risk of inheriting a mutation in a gene that places them at a higher risk of developing pancreatic cancer.

Familial pancreatic cancer occurs when two or more close relatives have both been diagnosed with pancreatic cancer (a parent and child or two siblings). About 5-10% of pancreatic cancer patients have another close relative who has also developed pancreatic cancer. The relatives of patients with familial pancreatic cancer have about a 9-fold increased risk of developing pancreatic cancer themselves (i.e. their risk of pancreatic cancer is 9 times higher than someone without such a family history.) Individuals with familial pancreatic cancer are more likely to have an inherited mutation in a gene that increases their risk of developing pancreatic cancer. However, shared environmental exposures such as cigarette smoking and poor diet can also cause pancreatic cancer to run in some families.

Most of the genes responsible for the clustering of pancreatic cancer are unknown, however, we do know that genes play a role in both the familial and non-familial forms of pancreatic cancer. There are both high-risk genes (genes that result in a >5% lifetime risk of pancreatic cancer) and low-risk genes which only slightly increase the risk of pancreatic cancer ( <2% lifetime risk). Our work has led to the identification of both high-risk and low-risk genes. High-Risk Genes include:

BRCA2: The BRCA2 gene got its name because it was the 2nd breast cancer gene identified. The team at Johns Hopkins, and others, has shown that 6%-12% of familial pancreatic cancer patients have an inherited defect in the BRCA2 gene. One particular defect in the BRCA2 gene (a mutation called 6174delT) is found in about 1% of individuals of Ashkenazi Jewish descent. This mutation may explain the higher rate of pancreatic cancer observed this group. It is estimated that the lifetime risk of pancreatic cancer in carriers of a BRCA2 gene mutation may be as high as 10%. Clinical testing is available for BRCA2. See below for more information on genetic testing.

ATM: ATM is a gene that has an important role coordinating DNA damage repair. ATM is also involved in preventing tumor development. Deleterious mutations of ATM gene were first reported by Dr. Roberts and his colleagues here at Johns Hopkins. ATM mutations were found in 166 familial pancreatic cancer patients compared to no ATM mutations in 190 spouse controls. Currently, ATM mutations are found in 1-5% of patients with pancreatic cancer. Clinical testing for ATM is currently available as part of most hereditary cancer panel tests.

PALB2: The PALB2 gene's official name is "partner and localizer of BRCA2". This gene contains the information to make the PALB2 protein. This protein works together with the BRCA2 protein to repair damaged DNA. The PALB2 protein is believed to stabilize the BRCA2 protein, allowing the BRCA2 protein to repair damaged DNA. We have recently discovered that about 3% 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. Clinical testing for PABL2 is currently available as part of most hereditary cancer panel tests.

p16/CDKN2A: The CDKN2A gene contains the sequence for two proteins, p16 and p14arf. Inherited mutations in the p16 protein are associated with an increased risk of pancreatic cancer and melanoma. Individuals with inherited mutations in the CDKN2A/p16 gene have a very high risk of melanoma and often come from families in which several individuals have developed melanoma. Individuals with inherited mutations in the CDKN2A/p16 gene also have a 15-35% lifetime risk of developing pancreatic cancer. Mutations in the CDKN2A/p16 genes are very rare and are thought to account for less than 1% of familial pancreatic cancer. Clinical testing for CDKN2A is available as part of most hereditary cancer panels.

STK11/LKB1: Inherited mutations in the serine/threonine kinase 11 gene, STK11, have been associated with Peutz-Jeghers syndrome, which is characterized by a special kind of polyp of the gastrointestinal tract and freckles (patches of hyper-pigmentation) on the inside of the mouth and lips. Individuals with Peutz-Jeghers syndome have a very high risk of developing pancreatic cancer, about 35% by age 60. Mutations in the STK11 gene are very rare and account for less than 1% of familial pancreatic cancer. Clinical testing for STK11 is available.

PRSS1: The PRSS1 gene is 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 gene are extremely rare and account for <1/2% of familial pancreatic cancer. Clinical testing for PRSS1 is available.

Currently, there are no established clinical guidelines for the management of individuals with a family history of pancreatic cancer. Certainly, we can give some common-sense advice. First, it is important that you discuss your family health history with your doctor. Second, if you have a family history of pancreatic cancer, and even if you do not, you should quit smoking if you currently do smoke, you should try to maintain a healthy body weight through diet and exercise, and the American Cancer Society recommends that we should all eat five servings of fruits and vegetables a day. Third, if you have a family history of pancreatic cancer you may also wish to consider joining a research study such as the National Familial Pancreas Tumor Registry at Johns Hopkins. This registry is aimed at better understanding of the causes of pancreatic cancer and why pancreatic cancer runs in some families. Finally, there are also clinical research trials, such as the CAPS ("cancer of the pancreas screening") studies, which evaluate the effectiveness of early detection screening for individuals with a family history of pancreatic cancer.

How to Join NFPTR

Clinical genetic testing is a medical test and should be conducted only after consulting with a trained genetic counselor and your health care providers.

There are things that you can do to reduce your risk of pancreas cancer:

Don’t Smoke: 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. Smoking rates among African American adults historically have been higher than among the general U.S. population. However, in recent years smoking rates for blacks and whites are similar. Cigarette smoking is the most preventable cause of pancreatic cancer.

Eat Healthy & Maintain a Healthy Weight: 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. In addition, the risk of pancreatic cancer increases with body mass. You should aim to maintain a healthy weight. Through eating a balanced, healthy diet, and managing your weight, you can also reduce your risk of type II diabetes.

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. Diabetes can sometimes be caused by pancreatic cancer.

Limit Alcohol Intake: Heavy alcohol use can lead to chronic 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 and African Americans are at the highest risk of developing pancreatitis of any racial group.

Clinical tests are tests ordered by physicians and/or other health care providers with the purpose of guiding medical care. Because clinical treatment decisions are based upon these tests, the federal government tightly regulates all clinical tests to make sure only laboratories with strict quality control procedures offer these tests. ONLY TESTS THAT MEET THESE REGULATIONS ARE CLINICALLY APPROPRIATE. If you are interested in learning if clinical genetic testing is right for you please contact your health care provider. Our registry runs research testing; research testing refers to experiments performed in a research laboratory. These tests are not approved for use in making individual level treatment decisions. As such, research test results are typically not given to study participants.