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Update: Genetic causes of hereditary pancreatic cancer: BRCA and beyond

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Contents

At a glance Clinical trials                       
Beyond       Guidelines            
Genes associated with pancreatic cancer Questions to ask your doctor          
What does this mean for me? Resources and references


UPDATE AT A GLANCE

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 .

  • About 3-10 percent of people with pancreatic cancer have a family history of the disease. 
  • Inherited mutations in and are the most common cause of familial pancreatic cancer. Together, about 6 percent of all pancreatic cancer patients have an in or .
  • Almost 14 percent of people with pancreatic cancer have a mutation.
  • Studies looking at patients who do not have a family history of pancreatic cancer have found that 4-11 percent have an in a gene associated with pancreatic cancer.

Beyond

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 , , , CDKN2A, , , , , and .

Of these genes, panel testing has shown that:

  • Mutations in are found in 2-3 percent of pancreatic cancer cases.
  • Mutations in genes (, , , and ) are found in <1 percent of cases.
  • Mutations in other genes (CDKN2A, , and ) 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 , suggesting the importance of family history. Being diagnosed at a younger age was also associated with an increased likelihood of having a mutation.

Genes associated with hereditary pancreatic cancer and risk

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
           Unclear Breast
    2-4 times Breast, ovarian,
3-8 times Breast, ovarian, , melanoma
CDKN2A 13-22 times    Melanoma
, , ,  
()
Up to 9 times Colorectal, endometrial (uterine), ovarian,
     Unclear Breast
( 132 times    Breast, gastrointestinal, gynecological
Source: Robert Pilarski, MS, LGC, MSW, LSW, ASCO June 2019

Summary:

In addition to mutations in and , 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 . Those who test positive for an 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.

What does this mean for me?

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.

Conclusions:

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 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 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

people newly diagnosed with cancer

people with pancreatic cancer

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Expert Guidelines
Expert Guidelines

National Comprehensive Cancer Network (NCCN) Guidelines

The NCCN recommends the following screening for people at increased risk for pancreatic cancer: 

  • Discuss the benefits and risks of screening with their doctor. Screening should be performed by a facility that is experienced with screening for pancreatic cancer. The recommended age for considering screening depends on a person’s family history of pancreatic cancer and varies by type of gene mutation.
    • Consider screening with magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic  (EUS).
    • Consider participating in a pancreatic cancer screening study.

The NCCN recommends that people with inherited mutations in the following genes (with or without a family history of cancer) "consider pancreatic cancer screening" with MRCP or EUS:

  • : (): Consider pancreatic cancer screening by MRCP or EUS every 1-2 years, beginning at ages 30-35 or 10 years younger than the earliest pancreatic cancer in the family.
  • CDKN2A: Consider pancreatic cancer screening beginning at age 40 or 10 years earlier than the earliest pancreatic cancer diagnosis in the family.

NCCN guidelines recommend that people with an in one of the following genes and a family history of cancer "consider pancreatic cancer screening" with MRCP or EUS, beginning at age 50 or 10 years earlier than the earliest pancreatic cancer diagnosis in the family: 

The NCCN does not currently recommend pancreatic cancer screening for people with the above mutations who do not have a family history of cancer. 

American Society for Gastrointestinal Endoscopy (ASGE) Guidelines

In February 2022, the ASGE released updated guidelines on pancreatic cancer screening for people with a or mutation. These guidelines recommended:

  • All patients with a mutation, regardless of family history of pancreatic cancer, should undergo annual screening for pancreatic cancer with MRI/MRCP or EUS, beginning at age 50 (or 10 years earlier than the earliest pancreatic cancer in the family).  

Updated: 07/03/2022

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network has guidelines on who should undergo genetic counseling and testing. The NCCN recommends genetic counseling and testing for anyone diagnosed with pancreatic cancer, using a comprehensive gene panel for .

Updated: 12/04/2021

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Should I have genetic testing for an
  • 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?

Open Clinical Trials
Open Clinical Trials

The following studies are looking at risk management for pancreatic cancer:

  • NCT04970056: Pancreatic Cancer Early Detection for People at High Risk (PRECEDE). The study will collect clinical information, family history, and samples (blood, saliva or cheek swab) from people and families at risk for pancreatic cancer.
  • NCT02000089: Pancreatic Cancer Screening Study (CAPS5). CAP5 is a study looking at screening for early cancer in people with an elevated lifetime risk of developing pancreatic cancer who are undergoing screening with endoscopic , MRCP or
  • NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High-Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer. Magnetic Resonance Imaging and Magnetic Cholangiopancreatography (MRI/MRCP) will be utilized to screen for pancreatic cancer or precursor lesions.
  • NCT02478892: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk. The study is a , observational study evaluating the utility of endoscopic or for the identification of preneoplastic and neoplastic pancreatic lesions in patients at high risk for pancreatic cancer, specifically those with BRCA1/2, or mutations.
  • NCT03568630: Blood Markers of Early Pancreas Cancer. Identifying biomarkers of early pancreatic ductal () could facilitate screening for individuals with higher-than-average risk, expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.
  • NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High-Risk Individuals. The goal is to screen for pancreatic cancer in individuals with a strong family history or genetic risk using Magnetic Resonance Imaging and Magnetic Cholangiopancreatography (MRI/MRCP).

A number of other clinical trials for pancreatic cancer screening and prevention may be found here.

Updated: 09/18/2024

Open Clinical Trials
Open Clinical Trials

The following are treatment studies enrolling people diagnosed with pancreatic cancer:

The following are vaccine studies enrolling people with pancreatic cancer:

  • NCT05111353: Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery. This study will look at the safety of an neoantigen vaccines in pancreatic cancer patients following chemotherapy. Participants will be placed in one of two groups. Group 1 will receive the vaccine following chemotherapy and surgery. Group 2 will receive the vaccine after  chemotherapy and before surgery.

Other clinical trials for people with pancreatic cancer can be found here.

Updated: 08/15/2023

Open Clinical Trials
Open Clinical Trials

The following studies are looking at treatment for people with advanced

 

Updated: 02/01/2024

Peer Support
Peer Support

The following organizations offer peer support services for people with or at high risk for pancreatic cancer:

Updated: 08/23/2022

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