Pancreatic Cancer and Genetics: Is There Genetic Testing for Pancreatic Cancer Patients?

Posted On Jan 10, 2020

Topic: Precision Medicine

According to the National Comprehensive Cancer Network (NCCN)’s 2019 Clinical Practice Guidelines, all pancreatic cancer patients should undergo genetic or germline testing for inherited genetic mutations, regardless of family history. Under these new recommendations, this testing should be done by a physician and the cost should be covered by insurance. The Lustgarten Foundation also encourages genetic testing, as there are options for screening programs if this testing demonstrates an inherited mutation.

Germline Testing for Inherited Risk

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene.

A germline (genetic) mutation is an inherited mutation, passed down from your parents. These germline mutations are likely to be important for pancreatic cancer development. About 10% of pancreatic cancer patients carry an inherited, germline mutation, which can increase the risk of certain cancers, including not only pancreatic cancer, but also breast, ovarian, and prostate cancers. Six genes in particular contain mutations that may be passed down in families and increase a person’s pancreatic cancer genetic risk; BRCA1, BRCA2, CDKN2A, TP53, MLH1 and ATM.

If someone does have an inherited risk, there may be options for more frequent screening to identify cancer or pre-cancer at an earlier stage. The GENERATE (GENetic Education, Risk Assessment, and TEsting) Study ( is for people who have a close relative with pancreatic cancer that was caused by an inherited mutation in a gene.  Funded by The Pancreatic Cancer Collective, an initiative of the Lustgarten Foundation and Stand Up To Cancer, the study provides genetic education and testing in people’s homes. The study is recruiting up to 1,000 participants from families with a germline genetic mutation in one of the following: APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11 or TP53. Participants will mail in a saliva sample and receive genetic testing at no cost. They will also be required to complete a series of four short follow-up questionnaires. Local genetic counseling and support services will be provided to everyone in the study.

Anyone who would like genetic testing performed, but does not qualify for the GENERATE Study, can purchase this service through Color Genomics ( or Myriad Genetics (

Molecular Profiling for an Informed Treatment Plan

Molecular profiling offers a blueprint of what’s happening in a tumor by identifying somatic mutations.

Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations may have the ability to cause cancer.

Molecular profiling tests analyze DNA, RNA, and protein in cancer cells to gain information that can be used to inform treatment decisions. Some molecular profiling tests may use one, two, or a combination of technologies to uncover information about the tumor. The findings are then used to identify new treatment programs for patients, which may include off-label use of medications that treat other cancers. The results can also be used to recommend enrollment in clinical trials testing new therapies.

For pancreatic cancer, there are two key examples of how molecular profiling can identify patients who are likely to respond to a given therapy: BRCA and MSI.

In human cells, both normal activities and environmental factors such as radiation can cause DNA damage. When normal DNA repair processes fail, irreparable DNA damage may occur.  This can eventually lead to cancer. BRCA1 and BRCA2 help repair damaged DNA.  Approximately 3 to 5 percent of pancreatic cancer patients carry mutations in either BRCA1 or BRCA2.  There is also a concept called BRCAness, which involves mutations in other key BRCA-related genes such as PALB2, ATM, or CHK2.  When you include these other BRCA-related genes, the target population in pancreatic cancer could be as high as 17 percent.

PARP (poly ADP-ribose polymerase) is an enzyme that plays a significant role in DNA repair. In patients who have defects in the ability of their cells to repair DNA, such as mutations in the BRCA genes, their cells are unable to repair these DNA breaks.  If a patient with a BRCA mutation receives a PARP inhibitor, tumor cells die, and normal cells are spared.

Microsatellite instability (MSI) is a change that occurs in the DNA of certain tumor cells because of defects in DNA mismatch repair. MSI is found in 1 in 50 advanced pancreatic cancer patients. Keytruda® (pembrolizumab) is effective for some patients with pancreatic cancer with high MSI. Keytruda targets PD-1, a checkpoint protein on immune system cells called T cells, that normally prevents T cells from attacking healthy cells in the body. By targeting PD-1, this drug boosts the immune response against pancreatic cancer cells and can often shrink tumors. Keytruda is the first cancer drug based on a genetic characteristic, rather than tumor site, to be approved by the FDA for use in pancreatic cancer patients. The Lustgarten Foundation played a critical role in bringing this new treatment to patients by funding the research, encouraging patients to get tested, and funding patients’ testing to determine if their tumors are mismatch repair deficient.

Knowing patients’ tumor (somatic) mutations and genetic (germline) mutations will help their oncologists to create the most effective, customized treatment plan and will enable patients to alert family members so they can undergo genetic testing for pancreatic cancer and early detection screening.  Both are critical to gain an advantage against pancreatic cancer.

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