Article: Life with a high-risk pancreatic and melanoma cancer mutation

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What is this article about?

During a 2018 patient education event in the Netherlands, Amarensia Spruitenburg shared her journey that led to the discovery of her family’s hereditary cancer mutation in the CDKN2A gene. Inherited mutations in CDNK2A increase the lifetime risk of melanoma and pancreatic cancer.  

Impact of an inherited CDKN2A mutation on family

Even before knowing about her family’s inherited mutation, Amarensia experienced significant loss in her life. Her mother and aunt died at a young age. Her aunt died from pancreatic cancer. Years later, her 49- year-old sister was also diagnosed with pancreatic cancer and died just a month later. Shortly after her sister’s death, her brother suggested they contact a clinical genetics center.

After genetic testing, Amarensia and her brother tested positive for an inherited mutation in CDNK2A. The CDNK2A gene makes instructions for two proteins, one of which is called p16. The mutation in Amarensia’s family, often called the p16-Leiden mutation, is commonly found in people from the Netherlands. Gene mutations that are found mainly in people of the same ethnic background are known as founder mutations.

Hereditary cancer and CDNK2A

CDKN2Awas the first familial melanoma gene identified by researchers in 1994. It accounts for many cases of familial melanoma. More specifically, people with an inherited mutation in CDKN2A have Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome. CDKN2A is the most common gene associated with FAMMM.  People with FAMMM usually have a personal or family history of more than 50 moles, melanoma and/or pancreatic cancer.

The lifetime risk of melanoma for people with a CDKN2A mutation ranges from 28 to 76 percent compared to 2.5% in the general population. Some of this variation is due to differences in UV exposure based on geographic location.  For instance, lifetime melanoma risks for Australians with CDKN2A mutations are highest (91%) compared to other geographic regions.  Both Amarensia and her sister developed melanoma.

The lifetime risk of pancreatic cancer for people with a CDNK2A mutation is 15 percent or higher compared to just under two percent for the general population.

You can find more information on CDKN2A mutations here.

Other inherited mutations also increase the risk of melanoma and/or pancreatic cancer. The increase in risk varies between genes. Most of the genes listed below have a lower risk of pancreatic cancer and melanoma than the risk associated with CDKN2A mutations

Total removal of the pancreas

Tragically, Amarensia’s brother was diagnosed with pancreatic cancer and died three years later. Five years after her brother’s death, during an endoscopic ultrasound screening for pancreatic cancer, doctors discovered two spots on Amarensia’s pancreas, one in the middle and another on the tail, the thinner tip of the pancreas.

Given her family history, Amarensia’s doctor recommended removing the entire pancreas, sometimes called a total pancreatectomy. This surgical procedure removes the pancreas as well as other organs and tissues, including:

• part of the stomach
• the first part of the small intestine, called the duodenum
• the end of the bile duct
• the gallbladder
• the spleen
• nearby lymph nodes

The surgeon reconnects the remaining parts of the stomach, bile duct and small intestine. This allows food and fluids needed to digest food to flow into the small intestines.

While there may be other reasons for removing the pancreas, this surgery may also be performed to prevent pancreatic cancer in patients with precancerous conditions.

After her surgery, Amarensia’s doctors initially told her that only one tumor was found in her pancreas. However, her doctor found that her pancreas was full of small lesions that likely would have developed into pancreatic cancer. Because of her cancer, Amarensia’s doctor recommended chemotherapy.

Recovery after complete removal of the pancreas

Spending a total of two weeks in the hospital, Amarensia’s recovery was long. Eating was difficult for her, so she had to get her nutrition from a tube in her vein. There were also complications.  After starting chemotherapy, she had a small bleed between the new connection between her stomach and intestine.  She had to spend additional days in the hospital but recovered quickly.

Overall, Amarensia’s quality of life had changed. Due to the function that the pancreas has in the body, when the pancreas is removed the person immediately develops type 1 diabetes. People with type 1 diabetes need to take insulin every day to help manage their blood sugar levels. Since Amarensia had her pancreas removed, she needs to take insulin for the rest of her life.

Even though Amarensia’s familial CDKN2A mutation led her to undergo the difficult decision to remove her pancreas, it also gave her the opportunity to focus on living with fewer concerns about her risk for pancreatic cancer.

Although living with diabetes was scary, Amarensia learned that she could do the activities that she loved with the help of dieticians.  

She is retired now and spends time hiking and biking with her partner in Europe.  

Why is this article important?

Pancreatic cancer is often diagnosed at an advanced stage, making it challenging to treat. Despite the difficulties that Amarensia lived through, her story shows that knowing you have an inherited mutation that increases your cancer risk can help you make informed decisions to find cancer early or reduce your risk.

The XRAY report "Benefit of pancreatic cancer screening" reviewed a study on the advantages of pancreatic cancer screening on BRCA1 and BRCA2 mutation carriers. While only a few pancreatic cancers were detected in the study, 75 percent were found at an early stage when they could be surgically removed.

Research on cancers like pancreatic cancer and melanoma is crucial, as it helps to improve screening methods while leading to earlier detection, better treatment outcomes and increased survival rates for families like Amarensia’s.

What does this mean for me?

Inherited mutations in CDKN2A increase the lifetime risk of melanoma and pancreatic cancer.  

Pancreatic cancer is often found at later stages and is harder to treat but screening for pancreatic cancer is now available for some people at high risk. When pancreatic cancer is caught earlier, patients have more treatment options, often including surgery.

If you have an inherited CDKN2A mutation, you should seek out a team of doctors with experience providing care to people at high risk for pancreatic cancer and melanoma. Discuss with your healthcare provider or genetic counselor the potential benefits, risks, costs and limitations of screening. 

If you are at high risk for pancreatic cancer and are interested in participating in a pancreatic cancer screening study, you can view our featured studies here.

Reference

Spruitenburg, A. M., & Vasen, H. F. (2024). The odyssee from surveillance to the detection of pancreatic cancer, total pancreatectomy, and its impact on life: Insights from a p16-Leiden pathogenic variant carrier. Familial Cancer, 23(3), 361–363. https://doi.org/10.1007/s10689-024-00385-0

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 11/22/24