What is familial pancreatic cancer?
Familial pancreatic cancer refers to 2 or more first-degree relatives (such as parents, brothers, sisters, or children) who have been diagnosed with pancreatic cancer and do not have other known inherited conditions for pancreatic cancer. As many as 10% of pancreatic cancers are familial.
There are several syndromes that can be passed down from parent to child that make a person more likely to get pancreatic cancer, including:
- Hereditary breast and ovarian cancer syndrome, which is caused by mutations (changes) in the BRCA1 or BRCA2 genes. Females with this syndrome have an increased risk for breast, ovarian, and pancreatic cancer. Males with this syndrome have an increased risk for prostate, breast, and pancreatic cancer.
- Familial atypical multiple-mole melanoma (FAMMM) syndrome, which is caused by mutations in the CDKN2A/p16 gene. People with this syndrome have an increased risk for melanoma and pancreatic cancer.
- Peutz-Jeghers syndrome (PJS), which is caused by mutations in the STK11/LKB1 gene. People with this syndrome have an increased risk for gastrointestinal polyps (called hamartomatous polyps) and gastrointestinal, pancreatic, breast, and other types of cancer.
- Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), which is caused by mutations in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. People with this syndrome have an increased risk for colorectal, endometrial (uterine), stomach, ovarian, urinary tract, and other types of cancer.
- PALB2 gene mutations, which cause an increased risk for pancreatic and breast cancer.
- Hereditary pancreatitis, which is caused by mutations in the PRSS1, SPINK1, CFTR (cystic fibrosis), or CTRC genes. People with this syndrome are at an increased risk for multiple episodes of pancreatitis and for pancreatic cancer.
What are the chances of inheriting a mutation that makes a person more likely to develop pancreatic cancer?
Both men and women can pass down mutations to their sons or daughters. For most of the syndromes listed above, it only takes 1 copy of the mutated gene to cause an increased risk for pancreatic and the other types of cancers mentioned for each syndrome.
Everyone has 2 copies of each gene, 1 from each parent. If 1 of your parents has a mutation, you have a 50% chance of having inherited the mutation, but also a 50% chance of not having inherited the mutation.
If you inherited the mutation from your parent, you are at a higher risk for cancer. If you did not inherit the mutation, you have the same risk for cancer as a person in the general population.Back to top
How are the mutations linked to pancreatic cancer found?
Mutations in the genes listed above can be found by testing a sample of DNA from either the blood or saliva. It is best to start genetic testing with a person in the family who has pancreatic cancer or any of the other related cancers listed above. Once a mutation has been found, other family members can then be tested for that same mutation.Back to top
What does a positive genetic test result mean?
A positive test result means that a disease-causing mutation has been identified. The person has inherited a syndrome that makes him or her more likely to get cancer.
It is important to understand that having a mutation does not mean that a person will definitely develop cancer; it just means that he or she has an increased risk of developing certain cancers. Some people with a mutation never develop cancer.Back to top
What does a “variant of uncertain significance” (or “ambiguous”) genetic test result mean?
Genes are written in chemical “letters” called bases. A wrong spelling of a gene can cause an increased risk of cancer. However, changes in the spelling of a gene may also be different in people without cancer. We are still learning which spellings are normal (harmless) and which can cause an increased risk for disease. These kinds of uncertain changes are called variants of uncertain significance.
If you have a variant of uncertain significance in a gene, we may not be able to tell you if it is a normal change or a disease-causing change. In some situations, we may be able to test your relatives for the variant or we may be able to do lab tests, but we still may not be able to tell if the variant will increase your risk for cancer. If you have a variant, we will make recommendations for cancer screening based on your family history.Back to top
What does a negative genetic test result mean?
A negative test result means that no mutation was found in the gene that was tested. This could mean any of the following:
- You could have a mutation in the gene that cannot be detected with the testing method that was used.
- No one genetic testing method can find all mutations.
- You could have a mutation in a different gene. Your genetic counselor may recommend testing for mutations in other genes that are also associated with pancreatic and other types of cancer.
- Your personal or family history of cancer could be related to other factors, such as age, environment, and chance.
- There is a genetic mutation in your family, but you did not inherit it.
How should people with a gene mutation manage their risk for related cancers?
The first goal for people with a mutation is to prevent cancers. The second goal is to find cancers at early enough stages so they can be treated.
The options for prevention and screening of cancers other than pancreatic cancer are different for each cancer and inherited syndrome listed earlier. Examples of prevention include surgical removal of the ovaries, uterus, or both. Examples of screening include yearly mammograms, breast magnetic resonance imaging (MRI), and colonoscopies. Your genetic counselor will give you information about the best prevention and screening options for you and your family.
Screening for pancreatic cancer is still being studied. At this time, screening for pancreatic cancer has not been shown to result in early diagnosis or decreased risk of death.
If you are at increased risk, you should watch for symptoms of pancreatic cancer, such as:
- Jaundice (yellowing of the skin and eyes, dark urine, and light, clay-colored stool)
- Generalized itching
- Pain in the upper abdomen and back
- Loss of appetite
- Unexplained weight loss
If you notice any of these symptoms, call your doctor.
If you are at an increased risk for pancreatic cancer, it’s especially important that you not smoke. If you want to quit, MSK’s Tobacco Treatment Program can help. You can reach them by calling 212-610-0507.Back to top
If I have a gene mutation, what are the risks to my children?
If you carry a mutation, each of your children (or future children) have a 50% (1 in 2) chance of inheriting the mutation. A person who inherits the mutation will also inherit the associated risks. It is important to remember that inheriting the mutation does not mean that a person will definitely develop cancer.Back to top
If I have a gene mutation, what are my options for having children?
If you have a mutation, you may want to learn about family planning options (starting a family or having more children). For example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called preimplantation genetic diagnosis (PGD). PGD is performed with in vitro fertilization (IVF), and may be an option for families who wish to have children without the mutation. To learn more, ask for a referral to a PGD/IVF specialist before attempting pregnancy.
Other possible family planning options include having children with the assistance of donor eggs or donor sperm and adoption.Back to top
What if I have questions?
If you have any questions or concerns, contact the MSK Clinical Genetics Service at 646-888-4050.Back to top