CDKN2A (p16INK4a) gene
Associated Syndrome Name: Melanoma-Pancreatic Cancer Syndrome (MPCS)
CDKN2A (p16INK4a) Summary Cancer Risk Table
|Cancer ||Genetic Cancer Risk |
CDKN2A (p16INK4a) gene Overview
Melanoma-Pancreatic Cancer Syndrome (MPCS) 1, 2, 3, 4
- Individuals with CDKN2A (p16INK4a) mutations have Melanoma-Pancreatic Cancer Syndrome (M-PCS). This condition has previously been known as Familial Atypical Multiple Mole Melanoma syndrome (FAMMM).
- Patients with M-PCS have a high risk of developing melanoma. Exact estimates of the melanoma risk associated with CDKN2A (p16INK4a) mutations vary over a wide range, with higher risks found in patients who have a previous family history of melanoma.
- Patients with M-PCS due to mutations in CDKN2A (p16INK4a) may also have a high risk for pancreatic cancer. This risk may not be present in all families with mutations in CDKN2A (p16INK4a), so concern about pancreatic cancer risk should be higher for patients who have a family history of this cancer.
- It has been suggested that patients with CDKN2A (p16INK4a) mutations have an increased risk for cancers other than melanoma and pancreatic cancer. In particular, there is evidence for an association with tobacco-related cancers such as lung, head and neck. The data are not conclusive at this time and there are currently no medical management recommendations that address these possible risks.
- Although there is a high risk for melanoma and pancreatic cancer in patients with M-PCS, it may be possible to reduce this risk with appropriate medical management, including increased attention to surveillance and lifestyle modifications. Guidelines from expert groups for the management of patients with high risks for these cancers are listed below. Since information about the cancer risks associated with CDKN2A (p16INK4a) mutations is relatively new, and there is uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics professionals who have expertise in this emerging area of knowledge.
CDKN2A (p16INK4a) gene Cancer Risk Table
|Cancer Type ||Age Range ||Cancer Risk ||Risk for General Population |
|Melanoma||To age 501, 3, 5||14%-50%||0.3%|
|To age 801, 3, 5||28%-76%||1.6%|
|Pancreatic||To age 752, 5||Up to 17%||0.7%|
CDKN2A (p16INK4a) Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.
This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.
|Cancer Type ||Procedure ||Age to Begin ||Frequency |
(Unless otherwise indicated by findings)
|Melanoma||Education about the importance of skin protection, such as sun avoidance, protective clothing and sunscreen.6, 7||Infancy||Ongoing|
|Whole-body skin examinations conducted by the patient or family member.6, 7||10 years||Monthly|
|Clinical skin examinations by an appropriately trained provider, with consideration of whole-body photography and close-up photography of atypical nevi for ongoing comparison.6, 7||10 years||Every 6 to 12 months|
|Pancreatic||Consider available options for pancreatic cancer screening, including endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in screening for pancreatic cancer, preferably within research protocols.8, 9||Age 40, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family||Annually|
|Provide education about ways to reduce pancreatic cancer risk, such as not smoking and losing weight.8, 10||Individualized||Individualized|
Information for Family Members
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the CDKN2A (p16INK4a) gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.
Since there are screening and preventative measures recommended to begin in infancy or early childhood for individuals with CDKN2A (p16INK4a) mutations, consideration should be given to the possibility of mutation testing at young ages.
- Bishop DT, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002 94:894-903. PMID: 12072543.
- Vasen HF, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000 87:809-11. PMID: 10956390.
- Begg CB, et al. Genes Environment and Melanoma Study Group. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J Natl Cancer Inst. 2005 97:1507-15. PMID: 16234564.
- Helgadottir H, et al. High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families. J Med Genet. 2014 51:545-52. PMID: 24935963.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- Kefford RF et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999 17:3245-51. PMID: 10506626.
- Coit DG et al. NCCN Clinical Practice Guidelines in Oncology®: Melanoma. V 1.2020 Dec 19. Available at http://www.nccn.org.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
- Goggins M, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 69:7-17. PMID: 31672839.
- Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology®: Pancreatic Adenocarcinoma. V 1.2020. Nov 26. Available at http://www.nccn.org.
Last Updated on 10-Sep-2020