|At a glance||Clinical trials|
|Genes associated with pancreatic cancer||Questions to ask your doctor|
|What does this mean for me?||Resources and references|
This update is about:
Inherited mutations in pancreatic cancer genes and the importance of identifying patients who have them.
Why is this update important?
Between 10–20 percent of all pancreatic cancer is thought to be due to an inherited mutation.
- About 3-10 percent of people with pancreatic cancer have a family history of the disease.
- Inherited mutations in BRCA1 and BRCA2 are the most common cause of familial pancreatic cancer. Together, about 6 percent of all pancreatic cancer patients have an inherited mutation in BRCA2 or BRCA1.
- Almost 14 percent of Ashkenazi Jewish people with pancreatic cancer have a BRCA mutation.
- Studies looking at patients who do not have a family history of pancreatic cancer have found that 4-11 percent have an inherited mutation in a gene associated with pancreatic cancer.
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:
- Mutations in ATM are found in 2-3 percent of pancreatic cancer cases.
- Mutations in Lynch syndrome genes (MLH1, MSH2, MSH6, and PMS2) are found in <1 percent of cases.
- Mutations in other genes (CDKN2A, PALB2, and STK11) are found in fewer than < 1 percent of cases.
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|
Source: Robert Pilarski, MS, LGC, MSW, LSW, ASCO June 2019
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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This article is relevant for:
People diagnosed with pancreatic cancer
This article is also relevant for:
People with a genetic mutation linked to cancer risk
Pancreatic cancer survivors
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Genetic Counseling and Testing Guidelines:
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.
Pancreatic cancer screening Guidelines:
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
- International Cancer of the Pancreas Screening Consortium (ICPSC) recommends endoscopic ultrasound and/or MRI for anyone who has:
- an STK11 mutation.
- a BRCA1, BRCA2, MSH1, MSH2, MSH6 PMS2 or CDKN2A mutation and a first-degree relative with pancreatic cancer.
- a first-degree relative and one other relative with pancreatic cancer.
- The ICPSC has not reached a consensus on the age(s) when screening should begin.
American College of Gastroenterology guidelines:
- The American College of Gastroenterology agrees with the ICPSC guidelines and also suggests that people with a mutation in BRCA1, BRCA2, PALB2, ATM, MSH1, MSH2, MSH6 or PMS2 and a first- or second-degree relative be offered screening.
- They recommend endoscopic ultrasound and MRI starting at age 50 or 10 years before the earliest diagnosis of pancreatic cancer in the family except for people with STK11 mutations, who should begin screening at age 35.
- Should I have genetic testing for an inherited mutation?
- I had genetic testing in the past, should I have additional testing?
- Should I have pancreatic cancer screening?
- Will my insurance pay for pancreatic cancer screening?
Studies enrolling people diagnosed with pancreatic cancer
- NCT03565991: A Phase II Study to Evaluate the Safety and Anti-tumor Activity of Avelumab in Combination with Talazoparib in Patients with a BRCA or ATM Mutation. (NOTE: The ATM arm of this study is closed). This study is looking at how well two cancer drugs work together to treat certain advanced cancers.
- NCT03337087: Chemotherapy/PARP Inhibitor Combination for Patients with Metastatic Pancreatic, Colorectal, Gastroesophageal or Biliary Cancer. This clinical trial studies a combination of drugs to learn the best dose, side effects and how well they work together for treating patients with pancreatic, colorectal, gastroesophageal or biliary cancer that has spread to other areas of the body.
- NCT03668119: A Study of Nivolumab Combined with Ipilimumab and Nivolumab Alone in Patients with Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden. This study is researching a combination of two immunotherapy drugs for advanced solid tumors that contain a tumor biomarker known as "High Tumor Mutation Burden" (TMB-H). The researchers are studying whether treatment of these tumors with a combination of the drugs nivolumab plus ipilimumab is safe and effective compared with nivolumab alone.
Studies enrolling people at high risk for pancreatic cancer
- 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.