Hereditary pancreatic neuroendocrine cancer

Multiple endocrine neoplasia (MEN) disorders cause tumours in several endocrine glands. These can be either benign (non-cancerous) or malignant (cancerous). These disorders affect the endocrine system, which is made up of glands that produce hormones, and includes the pancreas.

There are five types of multiple endocrine neoplasia and each type is linked with specific tumours. MEN1 and MEN4 are linked with pancreatic NETs.

Multiple endocrine neoplasia type 1 (MEN1) is a rare condition caused by variants in the MEN1 gene. It is linked with pancreatic NETs, and with benign parathyroid and pituitary tumours (adenomas). Up to three quarters (75%) of people with MEN1 develop pancreatic NETs.

Multiple endocrine neoplasia type 4 (MEN4) may be even rarer than MEN1, although there hasn’t been much research into it. It is caused by variants in the CDNK1B gene. It is linked with pancreatic NETs, and with parathyroid and anterior pituitary tumours (adenomas). Pancreatic NETs are less common in people with MEN4 than in people with MEN1.

Monitoring if you have MEN1 or MEN4

People with MEN1 or MEN4 should have regular monitoring to check for tumours. Check-ups should include annual blood tests and MRI, EUS and/or CT scans every 1-3 years.

If doctors think you have MEN1 or MEN4, you should be referred for genetic testing. If you have a pancreatic NET and have had hyperparathyroidism or pituitary adenomas, you should also be referred for genetic testing. Read more about genetic testing.

Von Hippel-Lindau (VHL) syndrome is caused by a variant in the VHL gene. It can cause tumours to develop in different places in the body, including the central nervous system, kidneys, eyes and pancreas. Most tumours linked with VHL are not cancerous.

Around half of people with VHL may have cysts in the pancreas, which don’t usually cause any symptoms. Some cysts can become cancerous so cysts should be assessed to check the risk of them becoming cancer.

Up to 20 out of 100 people (20%) with VHL may develop one or more pancreatic NETs. These tumours are usually non-functioning. This means they don’t produce more hormones than normal and generally don’t cause hormone-related symptoms.

 Screening for people with variants in the VHL gene should begin from early childhood. The type of screening and how often you have it can vary. It will usually include an eye examination, blood or urine tests and an MRI or CT scan of the kidneys each year. Read more about screening and recommendations for VHL on the Genomics England website.

Tuberous sclerosis complex (TSC) is a rare genetic disorder linked to TSC1 and TSC2 gene variants. Up to 1 in 10 (10%) people who have a TSC2 gene variant develop a pancreatic NET. Tuberous sclerosis complex can also cause benign (non-cancerous) tumours in other parts of the body.

Neurofibromatosis type 1 (NF1) is a genetic disorder linked to NF1 gene variants. It is most commonly linked to changes in skin colouring (pigmentation) and benign (non-cancerous) tumours. A small number of people with NF1 may develop pancreatic NETs.