Causes of Neuroendocrine Tumors

What causes neuroendocrine tumors?

We don’t know what causes neuroendocrine tumors.  Most seem to develop sporadically. NETRF is actively researching the causes of NETs. Some risk factors for neuroendocrine cancers, however, can be passed down in families.

Inherited risk factors for NETs

Most cases of NETs are not associated with hereditary risk factors. Researchers estimate that inherited factors may be associated with 17% of PNETs26 and in 25% of pheochromocytomas and paragangliomas27. Other rates vary by primary site and subtypes of tumors.

Knowing you have an inherited genetic risk factor won’t always have an impact on your treatment plan, but it can affect how your doctor monitors your health. If a genetic mutation is confirmed, your doctor may order additional testing on a regular basis to look for other risks associated with that risk factor.

NameAssociated Syndrome(s) or ConditionsAffected Gene(s)Related NETs
MEN1: Multiple endocrine neoplasia type 128,29
  • Zollinger-Ellison syndrome30
  • Gastrinomas
  • Insulinomas
  • VIPomas
  • Glucagonomas
  • Somatostatinomas
  • NETs (broncho-pulmonary, gastric, thymic)
MEN2: Multiple endocrine neoplasia type 21
  • MEN2A Syndrome (Familial medullary thyroid cancer, hyperparathyroidism)
  • MEN2B Syndrome (Cutaneous lichen amyloidosis, Hirschsprung disease)
  • Pheochromocytoma
MEN4: Multiple endocrine neoplasia type 41
  • Overlaps with other MEN syndromes, primary hyperparathyroidism (PHPT)
CDKN1BNETS (pancreatic, lung, gastric)31
  • Von Hippel-Lindau Disease Von Hippel-Lindau Disease (Renal cell carcinoma and hemangioblastomas)
  • Pheochromocytomas
  • Paragangliomas
  • Pancreatic NETs
CGA: glucagon cell adenomatosis33
  • Mahvash disease
  • Paraganglioma
TSC: Tuberous sclerosis complex4
  • A wide spectrum of benign tumors, skin abnormalities and behavioral / cognitive problems
  • Pheochromocytoma
  • Pancreatic NETs4
NF1: Neurofibromatosis type 11
  • von Recklinghausen disease34
  • Neurofibromas
  • Peripheral nerve sheath tumors
  • Optic glioma
  • Paragangliomas
  • Pheochromocytomas
  • Gastrointestinal tract and pancreatic NETs3

How do you know if you have an inherited mutation?

The route to a clinical diagnosis for an inherited genetic mutation varies. In some cases, the presence of two or more associated medical conditions or syndromes can meet the criteria. A patient’s medical history, as well as their family’s medical history, is part of the evaluation process. Having a first-degree relative with a known mutation also plays an important role in establishing a clinical diagnosis.  

If a genetic mutation is suspected or known, your doctor may conduct a clinical evaluation that could include:

  • Blood or urine tests
  • Imaging test
  • Gene tests

There are many different types of gene tests using a range of technology. The types of gene testing kits advertised on TV or sold in the drug store will probably not help someone learn about their risk factors for NETS.  The type of genetic test your doctor would order would screen for a specific set of mutations, which may not be included on the panels of the tests available commercially.


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1Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335-1342.

3Sackstein PE, O’Neil DS, Neugut AI, et al. Epidemiologic trends in neuroendocrine tumors: an examination of incidence rates and survival of specific patient subgroups over the past 20 years. Seminars in Oncol. 2018;4(13):249-258.

4National Institute of Diabetes and Digestive and Kidney Diseases. Your digestive system and how it works. Accessed October 19, 2018.

26FSchernthaner-Reiter MH, Trivellin G, Stratakis CA. (2016). MEN1, MEN4, and Carney complex: pathology and molecular genetics. Neuroendocrinology, 103: 18e31.        

27National Cancer Institute. Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Health Professional Version. Accessed October 9, 2018.

28National Cancer Institute. Genetics of Endocrine and Neuroendocrine Neoplasia (PDQ®)–Health Professional Version. Accessed October 9, 2018.

29Cancer.NET, (ASCO® Patient Information). Multiple Endocrine Neoplasia Type 1. Accessed October 10,2018.

30National Institute of Diabetes and Digestive and Kidney Diseases. Zollinger-Ellison syndrome. Accessed October 10, 2018.

31Alrezk R, Hanah-Shmouni F, Stratakis CA. MEN4 and CDKN1B mutations: The latest in MEN syndromes. Edocr Relat Cancer 2017. 24;(10):T196-208

32National Cancer Institute. Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Health Professional Version. Accessed October 9, 2018.

33Mete, O., Chetty, R. (2017). Pancreatic endocrine neoplasia: familial syndromes. Diagn Histopathol, 23:8, 378.

34Cives, M., Strosberg, J.R. (2018). Gastroenteropancreatic Neuroendocrine Tumors. CA Cancer J Clinical, 1-17.