What are genes?

Genes carry individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in pancreatic cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

Genetic mutations in certain types of genes are more likely to cause cancer. Oncogenes are genes that can change normal cells into cancer cells. An oncogene forms when mutations occur in a proto-oncogene. A proto-oncogene makes proteins that promote normal cell growth. Mutations in proto-oncogenes result in too much cell growth and can lead to cancer.

A tumor suppressor gene makes proteins that prevent tumor formation by limiting cell growth. Mutations in a tumor suppressor gene cause a loss of the ability to restrict tumor growth and, as a result, cancer can develop.

A mismatch repair gene makes proteins that repair DNA mistakes that occur as a cell divides. If one of these genes has a mutation, the mistakes cannot be repaired, leading to damaged DNA and an increased risk of cancer.

A person may either be born with a genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Somatic mutations can sometimes be caused by environmental factors, such as cigarette smoke. Most pancreatic cancers (about 90%) are considered sporadic, meaning that the damage to the genes occurs after a person is born, and there is no risk of passing on the gene to a person’s children. Inherited pancreatic cancers are less common (about 10%) and occur when gene mutations are passed within a family, from one generation to the next.

What are the chances a mutated gene is inherited?

Every cell usually has two copies of each gene: one inherited from a person’s mother and one inherited from a person’s father. Most types of hereditary pancreatic cancer follow an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a gene mutation also has a 50% chance of having the same mutation.

What is a person's average risk for pancreatic cancer?

A person with an average risk for pancreatic cancer has less than a 1% chance of developing pancreatic cancer sometime during his or her life.

How common is pancreatic cancer?

In 2008, an estimated 37,680 adults (18,770 men and 18,910 women) in the United States will be diagnosed with pancreatic cancer. It is estimated that 34,290 deaths (17,500 men and 16,790 women) from this disease will occur this year.

How can a person know if he or she has inherited a genetic mutation that increases his or her risk of pancreatic cancer?

Only genetic testing can determine whether a person has a genetic mutation. Most experts strongly recommend that people considering genetic testing first consult a genetic counselor. Genetic counselors are trained to explain the risks and benefits of genetic testing.

For more information, read Cancer.Net: Genetic Testing and Cancer.Net: What to Expect When Meeting With a Genetic Counselor.

How does a person know if pancreatic cancer runs in the family?

Pancreatic cancer runs in a family when two or more first-degree relatives (parents, brothers, sisters, children) are diagnosed with pancreatic cancer. This is sometimes referred to as familial pancreatic cancer. Families with three or more close relatives (first-degree relatives, grandparents, aunts, uncles, nieces, nephews, grandchildren, cousins) diagnosed with pancreatic cancer, and with one relative diagnosed before the age of 50, are also considered to have familial pancreatic cancer.

What is a person's risk if pancreatic cancer runs in the family?

If a person has a first-degree relative with pancreatic cancer, his or her risk of developing pancreatic cancer is significantly greater than the average person's risk of pancreatic cancer. The National Institutes of Health (NIH) estimates that the risk of developing pancreatic cancer is increased 4 to 5 times for a person with one first-degree relative with pancreatic cancer, 6 to 7 times for a person with two first-degree relatives, and 32 times for a person with three first-degree relatives.

Which inherited genetic mutations raise the risk of pancreatic cancer?

There are several genes linked to an increased risk of pancreatic cancer. The most common hereditary cancer syndromes associated with pancreatic cancer risk are described below.

Hereditary pancreatitis (HP). People with HP have a 40% risk of developing pancreatic cancer. Pancreatitis is inflammation or swelling of the pancreas that causes severe abdominal pain. HP can begin in childhood and become worse over time. The gene most often associated with HP is called PRSS1, the role of which is not yet known. Mutations in two other genes, called SPINK1 and CFTR, have also been linked to HP; however, it is unknown if mutations in these genes cause an increased risk of pancreatic cancer. Genetic testing for mutations in the PRSS1, SPINK1, and CFTR genes is available for people who may have HP.

For more information, read the Cancer.Net Guide to Hereditary Pancreatitis.

Peutz-Jeghers syndrome (PJS). People with PJS have a 35% risk of developing pancreatic cancer. People with PJS often have multiple hamartomatous polyps, which are normal-appearing growths in the digestive tract that become noncancerous tumors. These polyps cause an increased risk of colorectal cancer. People with PJS also have increased pigmentation (dark spots on the skin) on the face and hands. The increased pigmentation often appears in childhood and fades over time. Women with PJS have about a 20% risk of developing ovarian cancer. Families with PJS also have an increased risk of breast, uterine, and lung cancers. The gene associated with PJS is called STK11. The STK11 is a tumor suppressor gene, and genetic testing for the STK11 gene is available.

For more information, read the Cancer.Net Guide to Peutz-Jeghers Syndrome.

Familial atypical multiple mole melanoma and pancreatic cancer (FAMMM-PC). FAMMM-PC is also known as melanoma-pancreatic cancer syndrome. People with FAMMM-PC have up to a 17% risk of developing pancreatic cancer. FAMMM-PC is associated with mutations in the CDKN2A gene. People who have mutations in the CDKN2A gene also have about a 70% risk of developing melanoma during their lifetime.

The CDKN2A (also called p16 and MST1) gene is a tumor suppressor gene. Genetic testing for mutations in CDKN2A is available, but testing is currently not recommended outside of clinical trials.

For more information, read the Cancer.Net Guide to Familial Malignant Melanoma.

Hereditary breast and ovarian cancer (HBOC) syndrome. The two genes are associated with HBOC, BRCA1 and BRCA2 (BRCA stands for BReast CAncer), are most often associated with an increased risk of developing breast and ovarian cancer for women and breast and prostate cancer for men. However, mutations in both genes have been linked to an increased risk of other types of cancer, including pancreatic cancer. The risk of pancreatic cancer for families with BRCA2 mutations is estimated to be up to 10 times greater than the average risk. There may also be a small increased risk of pancreatic cancer for families with BRCA1 gene mutations.  

For more information, read the Cancer.Net Guide to Hereditary Breast and Ovarian Cancer.

Hereditary non-polyposis colorectal cancer (HNPCC). HNPCC (sometimes called Lynch syndrome) causes less than 5% of hereditary pancreatic cancer cases. HNPCC is most commonly associated with an increased risk of colorectal cancer. The risk of colorectal cancer for families with HNPCC is 80%, which is several times greater than the average risk. People with HNPCC also have an increased risk of cancers of the stomach and small intestine. Women with HNPCC have about a 9% to 12% risk of developing ovarian cancer and a 20% to 60% risk of uterine cancer. There may also be an increased breast cancer risk for families with HNPCC.

Mutations in the MLH1, MSH2, MSH6, and PMS2 genes are the most frequent cause of HNPCC. The genes associated with HNPCC are mismatch repair genes. Although multiple genes have been linked to HNPCC, most families with HNPCC have a mutation in only one of the genes. Genetic testing is available for the MLH1, MSH2, and MSH6 genes. The PMS2 gene is only tested as part of a clinical trial.

For more information, read the Cancer.Net Guide to Hereditary Non-Polyposis Colorectal Cancer.

Other forms of familial pancreatic cancer. Research to find other genes associated with familial pancreatic cancer is ongoing. Families with multiple instances of pancreatic cancer who do not have any other signs of a specific hereditary cancer syndrome may consider participating in clinical trials to help find additional hereditary pancreatic cancer genes. A genetic counselor can help locate appropriate research studies.

Are there other genetic conditions associated with an increased risk of pancreatic cancer?

There may be additional hereditary cancer syndromes that increase the risk of pancreatic cancer, and anyone concerned about their family history should talk with their doctor or genetic counselor. As research continues, doctors may learn more about the causes of inherited pancreatic cancer.

Li-Fraumeni syndrome (LFS). People with LFS have up to a 50% chance of developing cancer by age 40 and a 90% chance of developing cancer by age 60. Some of the cancers most commonly associated with LFS are osteosarcoma (a type of bone cancer), soft tissue sarcoma, leukemia, breast cancer, brain cancer, and adrenal cortical tumors. An adrenal cortical tumor begins in the adrenal cortex, which is the outer layer of the adrenal glands. The adrenal glands are located on top of each kidney and are a part of the body’s endocrine (hormonal) system. Pancreatic cancer has occasionally been reported in such families, but the risk of developing pancreatic cancer is not known.

LFS is a rare condition. The gene associated with LFS, called p53, is a tumor suppressor gene. Testing for p53 gene mutations is available for families who may have LFS. Another gene, CHEK2, may cause LFS for some families. Testing for mutations in the CHEK2 gene is only available as part of a research study.

For more information, read the Cancer.Net Guide to Li-Fraumeni syndrome.

Familial adenomatous polyposis (FAP). People with FAP often develop hundreds to thousands of polyps (a growth in the colon or rectum) that are initially noncancerous, but there is almost a 100% chance that the polyps will develop into cancer if not treated. Most people with FAP develop polyps in their 20s or 30s, although polyps can be found as early as the teenage years, and colorectal cancer often develops by age 40. People with FAP also have an increased risk of other types of cancer including stomach, small bowel, pancreas, thyroid, and hepatoblastoma (liver cancer that usually occurs in early childhood).

Although FAP follows an autosomal dominant inheritance pattern, approximately 30% of people with FAP have no family history of the condition. FAP is caused by a mutation on the APC gene, which is a tumor suppressor gene. Genetic testing for the APC gene is available.

For more information, read the Cancer.Net Guide to Familial Adenomatous Polyposis.

What is a person's risk level?

In addition to family history, other environmental and lifestyle factors may increase the risk of pancreatic cancer. Discussing family history and personal risk factors with a doctor can help a person better understand his or her risk. People with a higher than average risk may benefit from genetic counseling and early detection strategies. There is no standard procedure for screening either the general population or individuals with an increased risk of pancreatic cancer. However, researchers are exploring high resolution computed tomography (CT or CAT) scanning, endoscopic ultrasound, and endoscopic retrograde pancreatocholangiography (also called endoscopic retrograde cholangiopancreatography or ERCP) as possible screening methods. Read more about possible screening methods in the Current Research section of the Cancer.Net Guide to Pancreatic Cancer.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to pancreatic cancer cannot predict that a person will develop cancer. Controllable risk factors, such as eating a balanced diet, maintaining a healthy weight, exercising, limiting alcoholic beverages, and avoiding tobacco products also play a role. Smoking is the biggest controllable risk factor for pancreatic cancer. Some people who develop pancreatic cancer have few known risk factors. Research continues to help doctors better understand the risk between genetic mutations and pancreatic cancer. Talk with a doctor for more information about risk factors and prevention for pancreatic cancer.

More Information

Cancer.Net Guide to Pancreatic Cancer

Additional Resources

Pancreatic Cancer Genetic Epidemiology Consortium

Listing of Pancreatic Cancer Family Registries