The CDKN2A gene makes proteins that work as “tumor suppressors.” Tumor suppressor proteins do that - they prevent uncontrolled cell growth and, therefore, “suppress” a tumor from forming. When individuals are born with a harmful mutation in the CDKN2A gene that prevents it from being able to make these proteins correctly, the person’s lifetime risk for developing certain cancers is increased. Harmful mutations in CDKN2A cause a condition called Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM). Due to its association with pancreatic cancer, this syndrome is now more commonly known as FAMMM-Pancreatic Cancer Syndrome.
In FAMMM-Pancreatic Cancer Syndrome, the risk of developing melanoma is between 28 and 76%. This risk varies among individuals and is influenced by other factors such as family history, geographic location where the person lives (i.e., a sunny climate vs. a rainy climate), and other genetic modifiers. The risk of developing melanoma in the general population is about 2.5%. Due to the highly increased risk in FAMMM-Pancreatic Cancer, people with CDKN2A mutations should have dermatology exams twice a year to monitor atypical moles.
The risk of developing pancreatic cancer in FAMMM-Pancreatic Cancer is at least 15%. This is in comparison to the general population risk of about 2%. Therefore, all people with CDKN2A mutations, regardless of whether or not they have family members with pancreatic cancer, should undergo pancreatic cancer surveillance for early detection. Pancreatic cancer surveillance is done by two different methods, either abdominal MRI/MRCP or endoscopic ultrasound (EUS). Pancreas imaging for people with CDKN2A mutations should be done every year. Pancreatic cancer screening should start by age 40, though people with a family history of pancreatic cancer under the age of 50 may need to initiate screening earlier.
Browse the links below to learn more about the CDKN2A gene:
FORCE (Facing Hereditary Cancer Empowered): https://www.facingourrisk.org
Cancer.Net (managed by the American Society of Clinical Oncology):
To find an inherited GI Cancer Genetics Clinic near you, check out the “Find a Clinic” page on the CGA-IGC website: https://www.cgaigc.com/find-a-clinic
The American College of Gastroenterology (ACG), the National Comprehensive Cancer Network (NCCN), and the American Gastroenterology Association (AGA) suggest that patients be cared for at expert centers that provide a comprehensive, multidisciplinary pancreatic cancer surveillance program. Many of these centers participate in consortiums that encourage the collection of standardized surveillance data to support research efforts to improve pancreatic cancer surveillance. You can find comprehensive GLOBAL resources for Pancreatic Surveillance Programs - including CGA-IGC Centers, International Cancer of the Pancreas Screening (CAPS) Consortium, and Pancreatic Cancer Early Detection (PRECEDE) Consortium on the CGA-IGC website here
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If you enjoyed this blog post, you might be interested in the following resources
1. On-demand Webinars FREE for CGA-IGC members. Not a member? Sign up here!
From 2023 with Barry Tong, Niharika Dixit, and Evan Walker discussing Optimizing access to genetic testing for patients with pancreatic cancer. Webinar / Blog
2. Podcasts OPEN ACCESS
From 2022 with Michael G. Goggins, M.B.B.CH., M.D., and Beth Dudley Yurkovich, MS, MPH, CGC, speaking about The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival. Podcast
From 2022 with Thomas (T.J.) Slavin, M.D.,FACMGG, Ph.D. and Bryson Katona, M.D., PhD, speaking about EUS-based Pancreatic Cancer Surveillance in BRCA1/BRCA2/PALB2/ATM Carriers Without a Family History of Pancreatic Cancer. Podcast