Neuroendocrine tumours, often referred to as NETs, emerge from neuroendocrine cells that play a crucial role in the regulation of hormones. These tumours can manifest in different organs, and their characteristics vary widely. While NETs are relatively rare compared to other cancers, their impact on patients can be significant, leading to various symptoms and complications.
The emergence of NETs can certainly involve genetic and environmental factors. Understanding the role of genetics is pivotal in unravelling the complexities of NET development. While many NETs occur sporadically, meaning without an identifiable cause, a subset is linked to hereditary factors.
In this article, we explore the intricate relationship between genetics, risks, and testing in the context of hereditary factors in neuroendocrine tumours. For more information and support, get in touch with NeuroEndocrine Cancer Australia’s NET cancer nurse line.
The hereditary nature of neuroendocrine cancer is a subject of scientific investigation. While most cases of NETs are sporadic, meaning they occur by chance, certain hereditary patterns and conditions are associated with an increased risk of developing NETs.
MEN1 is an autosomal dominant condition characterised by tumours in multiple endocrine glands, including the pancreas. Individuals with MEN1 mutations have an increased risk of developing pancreatic NETs.
Associated syndromes: MEN1, Zollinger-Ellison syndrome
Affected genes: MEN1
Related NETs: Gastrinomas, Insulinomas, VIPomas, Glucagonomas, Somatostatinomas, NETs (broncho-pulmonary, gastric, thymic)
MEN1 is an autosomal dominant condition characterised by tumours in multiple endocrine glands, including the pancreas. Individuals with MEN1 mutations have an increased risk of developing pancreatic NETs.
Associated syndromes: MEN2A Syndrome, MEN2B Syndrome
Affected genes: RET
Related NETs: Pheochromocytoma
MEN4 is an autosomal dominant condition, signifying that inheriting a single copy of the mutated gene from either parent can lead to the expression of the condition. This genetic syndrome is characterised by the development of tumours in various endocrine glands. Individuals with MEN4 mutations face an increased risk of developing neuroendocrine tumours, with manifestations across different endocrine organs.
Associated syndromes: Overlaps with other MEN syndromes, primary hyperparathyroidism (PHPT)
Affected genes: CDKN1B
Related NETs: NETs (pancreatic, lung, gastric)
VHL is an autosomal dominant genetic disorder involving mutations in the VHL gene.
Individuals with VHL disease are prone to the development of tumours and cysts in various organs, such as the kidneys, adrenal glands, and pancreas. The disease is marked by an increased risk of specific tumours, including renal cell carcinoma and hemangioblastomas in the central nervous system.
Associated syndromes: Von Hippel-Lindau Disease
Affected genes: VHL
Related NETs: Pheochromocytomas, Paragangliomas, Pancreatic NETs
GCA, or glucagon cell adenomatosis, is associated with mutations in genes like SDHD, SDHAF2, SDHC, and SDHB. It is characterised by the development of paragangliomas, which are tumours originating from the neuroendocrine cells. These tumours often affect the adrenal glands, leading to an overproduction of hormones and potential complications.
Associated syndromes: Mahvash disease
Affected genes: SDHD, SDHAF2, SDHC, SDHB
Related NETs: Paraganglioma
TSC is an autosomal dominant disorder involving mutations in either the TSC1 or TSC2 gene.
This complex condition is marked by the formation of benign tumours in various organs, including the brain, kidneys, heart, and skin. Patients with TSC may develop neuroendocrine tumours, particularly in the pancreas, contributing to the complexity of the disorder.
Associated syndromes: A wide spectrum of benign tumours, skin abnormalities, and behavioural/cognitive problems
Affected genes: TSC1, TSC2
Related NETs: Pheochromocytoma, Pancreatic NETs
NF1 is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Characterised by the development of neurofibromas, or tumours arising from nerve tissue, NF1 can affect multiple systems, including the skin, nervous system, and bones. Individuals with NF1 may also be at an increased risk of developing neuroendocrine tumours, adding to the spectrum of manifestations associated with this genetic condition.
Associated syndrome: von Recklinghausen disease
Affected gene: NF1
Related NETs: Gastrointestinal tract and pancreatic NETs
While hereditary NETs represent a minority of cases, their impact on affected individuals is substantial. Understanding the prevalence of hereditary patterns helps in identifying at-risk individuals and implementing targeted screening and preventive measures.
Here’s how hereditary vs sporadic cases differ between some of the conditions mentioned above:
Certain genetic factors and mutations have been identified in association with NETs. These include mutations in genes such as MEN1, RET, and others, depending on the specific type of NET.
Genetic factors can influence the risk and development of NETs by disrupting the normal regulation of cell growth and hormone production. Abnormalities in specific genes may contribute to the initiation and progression of NETs.
Genetic predisposition refers to an increased likelihood of developing a particular condition due to inherited genetic factors. In the context of NETs, individuals with certain gene mutations may have a predisposition to these tumours.
Several genes are associated with an increased risk of developing NETs, including MEN1, RET, VHL, and others. Understanding the specific genetic landscape aids in risk assessment and targeted management.
Genetic testing for NETs is typically recommended in individuals with a family history of NETs, especially in cases of known hereditary conditions like MEN1, MEN2 or VHL.
The genetic testing process involves obtaining a sample, usually through a blood test, and analysing specific genes for mutations. Results can provide valuable information for risk assessment and management.
Genomic studies will significantly advance our understanding of NETs. These studies will explore the entire genomic landscape, identifying key mutations and abnormalities associated with NET development.
Current genomic approaches in NET research involve precision medicine, tailoring treatment based on the genetic makeup of the tumour. This targeted approach holds promise for improved treatment outcomes.
Navigating the process of treating hereditary neuroendocrine tumours can be challenging. Seeking genetic counselling is vital to understand what genetic testing is and the impact of the results and outcomes. Fortunately, patients impacted by hereditary conditions can find solace and guidance through various support networks. Accessing support plays a pivotal role in managing the emotional and practical aspects of the diagnosis and treatment journey.
Here are some top tips if you’re at risk of or have a familial hereditary NETs:
Individuals with a family history of NETs require proactive management and monitoring. Regular screenings and surveillance help detect tumours at an early, more treatable stage.
Organisations like NeuroEndocrine Cancer Australia are committed to providing unwavering support for individuals affected by hereditary NETs. They offer an array of resources, educational materials, and foster a supportive community. NECA goes a step further by providing a dedicated NET cancer nurse line, accessible to patients and their families.
Engaging with online forums and support groups tailored specifically to individuals with hereditary NETs creates a valuable platform for sharing experiences, posing questions, and gaining insights from those who have traversed similar paths.
Exploring local support groups offers an additional avenue to connect with individuals facing similar challenges during diagnosis and treatment. Local gatherings provide opportunities for in-person interactions and the exchange of shared experiences.
Seeking counselling or psychosocial support services becomes essential to address the emotional impact and overall diagnosis and treatment process for individuals affected by hereditary NETs. Social workers, psychologists, or counsellors are adept at offering coping strategies and emotional guidance to navigate this intricate journey.
The interplay between genetics, risks, and testing in neuroendocrine tumours is a field that continues to evolve. As our understanding deepens, personalised approaches to screening, diagnosis, and treatment hold the promise of improved outcomes for individuals with hereditary predispositions to NETs.
Collaborative efforts between healthcare professionals, researchers, and advocacy organisations play a pivotal role in advancing the field and providing comprehensive support for affected individuals and their families.
