Neuroendocrine Tumor Causes and Risk Factors

Neuroendocrine tumors (NETs) develop from specialized neuroendocrine cells, which receive signals from the nervous system and release hormones that help regulate many important body functions, including breathing, digestion and metabolism. Neuroendocrine cells are found throughout the body, with high concentrations in the lungs, gastrointestinal tract and pancreas. 

NETs develop when neuroendocrine cells acquire genetic changes that cause them to grow and divide uncontrollably. In most cases, the exact cause is unknown. However, advancing age, certain inherited genetic syndromes and a family history of neuroendocrine tumors may increase the risk of developing neuroendocrine tumors.

Although NETs are considered uncommon, their incidence has increased significantly over the last several decades. According to the Neuroendocrine Tumor Research Foundation, more than 170,000 people in the United States are living with a neuroendocrine tumor.

What causes neuroendocrine tumors? 

NETs arise through a series of genetic and molecular changes that disrupt the normal processes controlling cell growth, division and survival. As these changes accumulate, abnormal neuroendocrine cells may form tumors that remain localized or spread to other parts of the body.

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Researchers do not fully understand why most neuroendocrine tumors develop. However, current evidence suggests that mutations in genes regulating cell growth, hormone production and DNA repair may contribute to tumor formation. Potential biological mechanisms involved in NET development include:

• Acquired genetic mutations – DNA changes that occur during a person’s lifetime can alter the normal behavior of neuroendocrine cells, allowing them to grow rapidly and form tumors.
• Disruptions in cellular growth pathways – Abnormalities in the molecular pathways that regulate cell growth, division and survival may contribute to tumor development.
• Changes in tumor suppressor genes – Alterations in genes that normally limit abnormal cell growth have been identified in some NETs.
• Abnormal cellular signaling – Researchers continue to study how disruptions in the signals that regulate neuroendocrine cell function and hormone secretion may influence tumor formation.

What are the risk factors for neuroendocrine tumors?  

Most NETs do not have a clearly identifiable cause. However, researchers have identified several characteristics and inherited conditions that may increase the likelihood of developing certain types of neuroendocrine tumors. These include:

• Increasing age – NETs are diagnosed most often in adults between the ages of 50 and 70.
• Multiple endocrine neoplasia type 1 (MEN1) – This inherited syndrome can significantly increase the likelihood of developing pancreatic neuroendocrine tumors and several other types of endocrine tumors.
• von Hippel-Lindau (VHL) disease – Individuals with this rare genetic disorder have an increased risk of developing certain NETs.
• Neurofibromatosis type 1 (NF1) – This inherited condition is associated with an elevated risk of several tumor types, including some neuroendocrine tumors.
• Tuberous sclerosis complex – Although uncommon, this genetic disorder may increase the likelihood of developing NETs.
• Family history of NETs – Having a close relative with a neuroendocrine tumor may increase risk, particularly when an inherited cancer syndrome is present.
• Certain stomach conditions – Chronic atrophic gastritis, pernicious anemia and other conditions that reduce stomach acid production may increase the risk of certain gastric NETs.

Which risk factors for neuroendocrine tumors are nonmodifiable?

Many recognized risk factors for NETs cannot be changed. Understanding these characteristics may help identify individuals who could benefit from genetic evaluation or, in some cases, specialized surveillance. Nonmodifiable risk factors for neuroendocrine tumors include:

• Age – Most NETs are diagnosed in adults older than 50, although some hereditary forms may develop earlier in life.
• Inherited genetic syndromes – Conditions such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, neurofibromatosis type 1 and tuberous sclerosis complex can significantly increase the risk of certain neuroendocrine tumors.
• Family history – A family history of NETs may indicate an inherited predisposition to developing these tumors.

Which risk factors for neuroendocrine tumors are modifiable?

Few risk factors for NETs can be changed. Unlike many common cancers, most neuroendocrine tumors are not strongly associated with preventable lifestyle behaviors. However, appropriate treatment of certain underlying stomach conditions may help reduce the risk of some gastric neuroendocrine tumors. Potentially modifiable risk factors include:

• Chronic atrophic gastritis and related stomach disorders – Appropriate evaluation and management may help address factors associated with certain gastric NETs.

Can neuroendocrine tumors be prevented?

Because the precise cause of most NETs is unclear, there is currently no proven way to prevent them. In addition, many neuroendocrine tumors develop in people with no identifiable risk factors. Although prevention is not currently possible in most cases, the following measures may help identify inherited risk, support earlier diagnosis and facilitate timely treatment:

• Understanding family medical history – Individuals who have one or more close relatives with NETs or inherited cancer syndromes should discuss their risk with a healthcare provider.
• Considering genetic counseling – Genetic counseling and testing may help identify inherited conditions associated with an increased risk of certain neuroendocrine tumors.
• Participating in recommended surveillance – Individuals with hereditary syndromes linked to NETs may benefit from periodic imaging studies, laboratory testing or other surveillance measures recommended by their healthcare team.
• Seeking prompt medical evaluation for persistent symptoms – Ongoing abdominal pain, flushing, chronic diarrhea, unexplained weight loss or other concerning symptoms should be evaluated by a physician.
• Managing chronic stomach disorders – Treatment of conditions such as chronic atrophic gastritis may help address factors associated with certain gastric NETs.

Find the help you need for neuroendocrine tumors at Moffitt Cancer Center 

Because NETs can arise in many different organs and vary considerably in their behavior, an accurate diagnosis is essential for selecting the most appropriate treatment. Moffitt’s multispecialty Gastrointestinal Oncology Program offers comprehensive evaluations and individualized care tailored to each patient’s specific type of neuroendocrine tumor and overall health.

If you would like to learn more about neuroendocrine tumor causes, risk factors or treatment options, you can request an appointment with a specialist at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.