From the Guidelines
The exact cause of neuroendocrine tumors (NETs) is largely unknown, but they likely develop from a combination of genetic mutations and environmental factors. Most NETs occur sporadically without a clear cause, though about 10-20% are associated with inherited genetic syndromes such as Multiple Endocrine Neoplasia type 1 (MEN1), Von Hippel-Lindau disease, Neurofibromatosis type 1, and Tuberous Sclerosis Complex, as noted in a study published in the Journal of the National Comprehensive Cancer Network 1. These genetic conditions involve mutations in tumor suppressor genes that normally prevent uncontrolled cell growth. In sporadic cases, mutations in genes like MEN1, DAXX, ATRX, and mTOR pathway genes have been identified. NETs develop from neuroendocrine cells, which are specialized cells found throughout the body that produce hormones in response to signals from the nervous system. When these cells undergo genetic alterations, they can multiply abnormally and form tumors. Some key points to consider include:
- Risk factors may include smoking (for lung NETs), chronic atrophic gastritis (for stomach NETs), and family history of NETs or related genetic syndromes, though for most patients, no clear risk factors are identified.
- A recent study published in Cancer Treatment Reviews in 2025 1 discussed the efficacy of streptozotocin in managing pancreatic neuroendocrine neoplasms, but did not provide information on the cause of NETs.
- The diagnosis and treatment of NETs are complex and depend on various factors, including the location and type of tumor, as well as the presence of symptoms or genetic syndromes.
- Further research is needed to fully understand the causes of NETs and to develop effective prevention and treatment strategies.
From the Research
Likely Cause of Neuroendocrine Tumors
The likely cause of neuroendocrine tumors (NETs) is not explicitly stated in the provided studies, but several factors are associated with their development:
- Genetic mutations, such as those found in multiple endocrine neoplasia type 1 (MEN-1) and type 2 (MEN-2), von Hippel-Lindau syndrome (VHL), tuberosclerosis, and neurofibromatosis syndromes 2
- Familial (inherited) syndromes, with MEN-1 being a significant contributor to the development of pancreatic NETs (PNETs) 3, 4, 2
- Sporadic mutations, with over 40% of sporadic PNETs harboring MEN-1 gene mutations 2
- Genetic alterations on chromosome 18, commonly found in small intestinal NETs 2
Associated Factors
Other factors associated with the development of NETs include:
- Increased awareness and improved detection methods, contributing to the rising incidence of NETs 5, 3
- Hormonal hypersecretion, leading to various clinical symptoms depending on the type of NET 5
- Tumor location, biochemical functional status, differentiation, initial staging, and response to treatment, which determine prognosis and survival in patients with NETs 5
Current Understanding
The current understanding of NETs is that they are a heterogeneous group of tumors with diverse primary tumor sites, functional status, and degrees of aggressiveness 6. While the exact cause of NETs is not fully understood, research continues to uncover the genetic and epigenetic factors contributing to their development 3, 2.