People with a genetic mutation linked to cancer risk
Pancreatic cancer survivors
An update on hereditary pancreatic cancer presented at the annual American Society of Clinical Oncology meeting covered genes and lifetime risk. The update emphasized that all pancreatic cancer patients should be offered genetic counseling and testing. Genetic test results may impact treatment, screening for other cancers and risk to family members. (11/26/19)
|At a glance||Clinical trials|
|Genes associated with pancreatic cancer||Questions to ask your doctor|
|What does this mean for me?||Resources and references|
Inherited mutations in pancreatic cancer genes and the importance of identifying patients who have them.
Between 10–20 percent of all pancreatic cancer is thought to be due to an inherited mutation.
Genetic panel testing, which looks for mutations in many genes at one time rather than just 1 or 2 at a time, has become more widespread in recent years and has led to a better understanding of which genes contribute to hereditary pancreatic cancer. Genes that are generally included in panel testing include BRCA1, BRCA2, ATM, CDKN2A, PALB2, STK11, MLH1, MSH2, MSH6 and PMS2.
Of these genes, panel testing has shown that:
One study found that 17 percent of patients with a family history of pancreatic cancer who had panel testing had an inherited mutation, suggesting the importance of family history. Being diagnosed at a younger age was also associated with an increased likelihood of having a mutation.
The lifetime risk for pancreatic cancer in the general population is 1.6 percent. The general population includes people with and without mutations. People with the following mutations had an increased risk for pancreatic cancer compared to people without a mutation.
|Gene||Increase in Pancreatic Cancer Risk Compared to
Someone Without the Mutation
|Other Associated Cancers|
|BRCA1||2-4 times||Breast, ovarian, prostate|
|BRCA2||3-8 times||Breast, ovarian, prostate, melanoma|
|MLH1, MSH2, MSH6, PMS2, EPCAM
|Up to 9 times||Colorectal, endometrial (uterine), ovarian, prostate|
|STK11 (Peutz-Jeghers Syndrome)||132 times||Breast, gastrointestinal, gynecological|
In addition to mutations in BRCA1 and BRCA2, numerous other inherited mutations increase the risk of pancreatic and other cancers. The National Comprehensive Cancer Network (NCCN) now recommends that all pancreatic cancer patients be offered genetic testing and counseling to determine whether they have inherited a germline mutation. Those who test positive for an inherited mutation may be eligible for different treatment options, such as PARP inhibitors or immunotherapies, and they may require screening for additional cancers. They may also need to alert their family members to the increased risks of certain cancers. Finally, the identification of mutations may make a patient eligible for specific clinical trials that are looking at targeted therapies for carriers of particular mutations.
If you have been diagnosed with pancreatic cancer, you should speak with your health care provider about receiving genetic counseling and testing to determine if you might carry an inherited mutation in a gene that is associated with hereditary pancreatic cancer. The results may be important for your treatment (including enrollment in clinical trials) and for your family.
If you have a family history of pancreatic cancer, you should speak with a health care provider about referral for genetic counseling and testing.
If you do not have pancreatic cancer but you know that you carry an inherited mutation in a relevant gene (see the table in this article) and you meet the screening guidelines outlined here, you should speak to your health care provider about receiving annual screening for pancreatic cancer.
Inherited mutations in a number of genes are associated with increase pancreatic cancer risk. It is important that people with pancreatic cancer are offered genetic testing and counseling to determine if they carry a germline mutation in one of these genes, as the results can impact treatment decisions, screening and risk management for other cancers, and family members’ risk. It is also important that people without pancreatic cancer but with an inherited mutation in a known pancreatic cancer risk gene are aware of screening guidelines and receive screening as appropriate.
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The National Comprehensive Cancer Network (NCCN) and The American Society of Clinical Oncologists (ASCO) recommend that all patients who are diagnosed with pancreatic cancer be offered genetic counseling and testing.
While numerous studies in the past have found no benefit (or an unclear benefit) to screening the general population for pancreatic cancer, recent research indicates that it is beneficial to screen people at higher risk.
International Cancer of the Pancreas Screening Consortium guidelines
American College of Gastroenterology guidelines:
NCT02000089: Cancer of the Pancreas Screening-5 Study (CAPS5). CAPS5 is a pancreatic cancer screening study for individuals at elevated risk for developing pancreas cancer.
NCT03693378. A Study of IMMray™ PanCan-d Test for Early Detection of Pancreatic Cancer in High-risk Groups. This study will validate and evaluate the performance of the IMMray PanCan-d test for pancreatic cancer diagnosis in comparison to standard of care imaging currently used in pancreatic cancer disease surveillance by the research sites’ institutions.
NCT03762590: The GENERATE (GENetic Education, Risk Assessment, and TEsting) Study. This study is for people who have a close relative with pancreatic cancer that was caused by an inherited mutation.