Causes & Risk Factors
Causes & Risk Factors
What can cause neuroendocrine cancers?
The exact causes of neuroendocrine cancer remain unknown, and the majority of cases occur sporadically without a clear cause.
Neuroendocrine cancers are a diverse group of tumours, and ongoing research is essential to uncovering more insights into their underlying causes, risk factors, and potential preventive measures.
Given neuroendocrine cancers are mostly misunderstood and complex, ongoing research is being conducted to better understand their underlying causes and to improve prevention, early detection, and treatment strategies.
If you have concerns about your risk of developing neuroendocrine cancer or are experiencing symptoms, it is crucial to consult with a healthcare professional for further investigation and guidance.
Risk factors that can influence neuroendocrine cancer development
While there are no apparent causes of neuroendocrine cancer, several risk factors have been identified. Risk factors are specific characteristics or exposures that increase an individual’s likelihood of developing neuroendocrine cancer.
In general, risk factors can be related to:
- Genetic factors like genetic mutations, or the presence of certain conditions and diseases
- Hereditary conditions such as multiple endocrine neoplasia type 1 (MEN–1), multiple endocrine neoplasia type 2 (MEN-2), Von Hippel-Lindau disease (VHL) and phacomatoses (neurocutaneous syndromes), which can be associated with multiple tumours.
- Conditions that affect stomach acid, such as pernicious anaemia and chronic atrophic gastritis
- Medical history, including the presence of other or past disorders
- Hormonal factors, including exposure to natural or introduced hormones
- Environmental factors, including prolonged exposure to ultraviolet (UV) radiation from the sun carcinogens and other substances in the environment
- Behavioural and lifestyle factors like diet and alcohol consumption
It’s important to note that having one or more risk factors does not guarantee that a person will develop cancer. However, risk factors can increase the chances. Conversely, many people diagnosed with cancer may not have any identifiable risk factors at all.
Hereditary conditions
Certain rare, inherited diseases can elevate the risk of developing neuroendocrine cancers. These conditions include multiple endocrine neoplasia (MEN 1, MEN 2), Von Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex, and neurofibromatosis.
In some instances, a family history of neuroendocrine cancer or related genetic conditions may increase the risk of developing these tumours.
Multiple Endocrine Neoplasia Type 1 (MEN1)
This rare genetic syndrome increases the risk of developing tumours in multiple endocrine glands, including the pancreas, parathyroid glands, and pituitary glands. Pancreatic NETs are a common feature of MEN1.
Multiple Endocrine Neoplasia Type 2 (MEN2)
This inherited syndrome is associated with the development of tumours in the thyroid gland and adrenal glands. MEN2 can be further divided into MEN2A and MEN2B, with MEN2A often linked to the development of medullary thyroid cancer and adrenal medullary NETs.
Von Hippel-Lindau (VHL) Syndrome
VHL is a hereditary condition that predisposes individuals to the development of tumours in various organs, including the central nervous system, eyes, inner ear, kidneys, adrenal glands and the pancreas, where pancreatic NETs, phaeochromocytoma and paraganglioma can occur.
Neurofibromatosis Type 1 (NF1)
This genetic disorder causes tumours to form on nerves, and in some cases, it may lead to the development of NETs in various organs.
SDH (succinate dehydrogenase) mutations
The gene encoding for the subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) is the most important contributor to hereditary malignant/metastatic pheochromocytoma (occurs in 10%) and paraganglioma (occurs in >50%).
Mutations in the genes for other SDH subunits – D and HAF2 also appear to be related to paragangliomas.
These mutations are autosomal dominant and can be inherited in 50% of offspring of affected patients. The risk of carrying these gene mutations and the development of pheochromocytomas or paragangliomas is variable and dependent on the ‘penetrance’ of the mutation.
Age and gender
Some types of neuroendocrine cancers are seen in particular for specific age groups and genders. For instance, neuroblastoma primarily affects young children, while non-functioning pancreatic NETs are more common in adults.
Neuroblastoma
This tumour is predominantly seen in young children, with the majority of cases diagnosed before the age of 5.
Exposure to carcinogens
Environmental factors, such as exposure to certain carcinogens, may play a role in the development of Neuroendocrine Cancer in some cases. However, the specific carcinogens that might be linked to NETs are not yet clearly identified, and more research is needed to establish direct links.
Viral infection
In some cases of Merkel cell carcinoma, infection with the Merkel cell polyomavirus (MCV) has been identified as a contributing factor. MCV is thought to integrate into the genome of Merkel cells, potentially leading to cancerous changes.
Sun exposure
Merkel cell carcinoma is also linked to excessive exposure to the sun and ultraviolet light. Additionally, it could also be triggered by the Merkel cell polyomavirus (MCV). Being aware of these risk factors can help individuals and healthcare professionals in the early detection and proactive management of neuroendocrine cancers and Merkel cell carcinoma.
Neuroendocrine cell hyperplasia
Hyperplasia is a condition in which there is an abnormal increase in the number of neuroendocrine cells in an organ or tissue. This hyperplasia may progress to the formation of NETs.
Immune system abnormalities
Disruptions in the immune system or immune suppression may contribute to the development of some NETs. For example, immunosuppression following organ transplantation can increase the risk of certain NETs.
Pre-existing conditions
Other factors: Some neuroendocrine cancers may be associated with pre-existing conditions, such as:
- Pernicious anaemia – A condition where the body can’t absorb enough vitamin B12 resulting in damage to the stomach lining, increasing risk of certain neuroendocrine cancers.
- Chronic atrophic gastritis – Long-term stomach inflammation can raise the risk of stomach neuroendocrine cancers.
- Peptic ulcers in the stomach or duodenum – may increase the risk of neuroendocrine cancer in these specific areas.
- Diabetes – individuals with diabetes may have a higher likelihood of developing pancreatic neuroendocrine cancer.
It is important to note that while these factors have been associated with an increased risk of developing neuroendocrine cancer, not everyone with these risk factors will develop the tumours, and many cases of neuroendocrine cancer occur without an identifiable cause.
Helpful Resources
Causes & Risk Factors
Age and Gender as Risk Factors for NETs
Booklets & Guides
Associated Conditions
Educational Videos
Brisbane NET Forum 2019 Hereditary Syndromes AMANDA LOVE
Causes & Risk Factors
Cellular Mutations in Neuroendocrine Cancer
Educational Videos, Explainer Videos
Genetic NETs explained
Causes & Risk Factors
Genetic Testing for Neuroendocrine Cancer
Causes & Risk Factors
Hereditary Factors in Neuroendocrine Tumours: Genetics, Risks, and Testing
Causes & Risk Factors
Immunological Factors in Neuroendocrine Tumour Development
Educational Videos
