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BRCA 1 and BRCA 2 Increases Pancreatic Cancer Risk

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If You Carry Mutated Genes BRCA 1 and BRCA 2, You Are At Increased Risk of Pancreatic Cancer

Written By Carlin Khulmann
October 8, 2018

BRCA 1 / 2 and Pancreatic Cancer

Angelina Jolie made headlines in 2013 when she announced that she underwent a preventative double mastectomy due to an inherited BRCA 1 mutation and her family history of breast cancer. Her openness led many women, especially those with a family history of breast or ovarian cancer, to think differently about their own potential risk and in some cases, consider genetic testing for the BRCA 1 and BRCA 2 gene mutations.

Receiving less public attention, however, is the relationship between inherited BRCA 1 and BRCA 2 mutations and increased risk for several other cancers besides breast and ovarian including pancreatic cancer.

While only 5-10% of all cancer cases are due to an inherited genetic (germline) mutation[1], individuals and families who carry germline mutations, like BRCA 1 and 2, have a greater risk for developing multiple cancers as compared with the general population.

There is currently no routine screening for pancreatic cancer, but understanding one’s individual risk, including a possible genetic predisposition, can help lead to early detection through customized screening and surveillance as guided by a physician specialist or team of specialists.

What Are BRCA 1 and 2 Mutations?

BRCA 1 and 2, or Breast Cancer 1 and 2, are human genes that make proteins that suppress tumors by repairing damaged DNA. When BRCA 1 and 2 genes become altered, or mutated, such that they no longer make proteins, or the proteins do not function properly, damaged DNA goes unrepaired. The accumulation of DNA damage can lead to cancer[2].

We all inherit two copies of each of our genes: one copy from our mother and one copy from our father, so a mutated BRCA gene can be inherited from either parent. Being born with a mutated BRCA 1 or BRCA 2 gene does not necessarily mean cancer will definitively occur in that individual.

BRCA 1 and 2 and Pancreatic Cancer

Average lifetime risk for developing pancreatic cancer is about 1 in 63 for men and 1 in 64 for women[3]. Research has shown that an inherited BRCA 1 mutation can double an individual’s risk for pancreatic cancer while an inherited BRCA 2 mutation can triple an individual’s risk for developing the disease[4].

When To Consider Genetic Testing

There are multiple personal and family history factors that could indicate the presence of an inherited BRCA 1 or BRCA 2 mutation. When one or more of these factors are present, a geneticist or genetic counselor can help patients make an informed decision about genetic testing. It’s always best to see a Genetic Counselor before getting Genetic Testing. The family history factors include the following:

Breast cancer diagnosed before age 50 (personal or family history)
Cancer in both breasts in the same woman
Both breast and ovarian cancers in either the same woman or the same family
Multiple breast cancers in the family
Male breast cancer or a relative with male breast cancer
A relative with ovarian cancer
A personal history of breast cancer and one or more relatives with breast cancer diagnosed at age 50 or younger, one relative with ovarian cancer, or two or more relatives with breast or pancreatic cancer
Ashkenazi Jewish ethnicity[5]

It is important to discuss individual risk factors with a genetic counselor or geneticist, who specialize in cancer genetics and are knowledgeable about the different types of genetic tests that are available.

For patients who have already been diagnosed with pancreatic cancer, knowing if it is related to a BRCA or BRCA mutation may impact their treatment. A type of targeted therapy called a PARP Inhibitor, for example, has shown promise in early phase clinical trials for patients with advanced pancreatic cancer who have a BRCA mutation. [6] Researchers and scientists continue to learn more about BRCA and other genetic mutations’ relationship to pancreatic and other cancers as well as how these cancers respond to different treatment.

Early Detection For Those Considered High-Risk

Individuals who test positive for a BRCA 1 or BRCA 2 mutation may benefit from enrollment in a program designed to surveil patients considered high-risk to ensure the earliest possible detection of cancer. The Seena Magowitz Foundation is familiar with two programs available for patients at increased risk for pancreatic cancer due to a family history of the disease or genetic predisposition such as a BRCA mutation:

1. The Pancreatic Cancer Early Detection/Prevention Program at HonorHealth in Scottsdale, AZ

2. The Anita Erickson Pancreatic Cancer Early Detection Program at Hoag in Newport Beach, CA

Both of the above programs assess patients’ risk for pancreatic cancer and develop personalized surveillance plans that may consist of special imaging tests, endoscopic ultrasound, and blood and urine tests to identify and monitor tumor markers. A multidisciplinary team of specialists in pancreatic cancer weigh-in on the best surveillance plan for each patient. The goal is to detect pancreatic cancer at the earliest possible stage when the chance for survival is the greatest.

Because research in this area is ongoing, de-identified patient information is submitted to a registry as shared by similar organizations in the nation to help improve pancreatic cancer early detection methods.