Neuroendocrine tumours (NETs) are a diverse group of cancers that arise from neuroendocrine cells—specialised cells responsible for producing hormones and regulating body functions. While some NETs are linked to inherited genetic syndromes, most occur sporadically with no clearly defined cause. As research into environmental and lifestyle influences grows, increasing attention is being paid to the role of potential carcinogens in the development of NETs.
Carcinogens are substances or exposures known to increase the risk of cancer by damaging DNA or disrupting normal cellular processes. For NETs, the evidence linking specific carcinogens remains limited and, in many cases, inconclusive.
However, understanding possible risks—particularly those related to environmental, occupational, and lifestyle factors—can help inform prevention strategies, policy decisions, and future research.
Neuroendocrine Cancer Australia (NECA), is dedicated to assisting individuals diagnosed with NETs and their loved ones. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients can engage with NECA’s comprehensive support and information by calling the NET nurse line.
Carcinogens are agents capable of causing cancer in living tissue. These may be chemical, physical, or biological in nature and can come from a wide variety of sources, including industrial activities, environmental pollution, processed foods, and some medical treatments. Not all exposures lead to cancer, but long-term or high-intensity exposure increases the likelihood of cellular changes that may result in tumour development.
The International Agency for Research on Cancer (IARC), part of the World Health Organisation, classifies carcinogens into several groups based on the strength of evidence:
NETs are less common, which presents a challenge when trying to definitively associate them with specific carcinogens. However, emerging research is beginning to explore these links in greater detail.
Certain occupations involve regular exposure to substances that may increase the risk of cancer, including NETs. Workers in industries dealing with heavy metals, organic solvents, pesticides, and chlorinated hydrocarbons may face higher risks due to repeated inhalation or skin contact with potentially carcinogenic substances.
Some studies have explored increased NET incidence among industrial workers, healthcare professionals (due to medical radiation), and agricultural workers. For instance, prolonged exposure to arsenic, cadmium, and formaldehyde has been suggested to disrupt endocrine cell function, although definitive causal links to NETs are still under investigation.
Long-term exposure to environmental pollutants has been associated with higher risks of various cancers. Airborne carcinogens such as benzene, diesel exhaust, and particulate matter may contribute to chronic inflammation and oxidative stress, which are known precursors to DNA damage.
Contaminants in drinking water—such as nitrates, heavy metals, and industrial runoff—are also under scrutiny for their potential role in gastrointestinal and pancreatic tumour risk. While studies specific to NETs are sparse, understanding how cumulative environmental toxin exposure affects neuroendocrine cells is an area of growing interest.
The consumption of processed meats, often preserved with nitrates and nitrites, has long been associated with an increased risk of colorectal and stomach cancers. These substances can form N-nitroso compounds, which are known carcinogens.
Some researchers have hypothesised that these compounds may also influence the risk of gastrointestinal NETs, particularly in the stomach and small intestine. While evidence remains inconclusive, ongoing studies are exploring whether frequent consumption of nitrate-rich foods might contribute to the development of hormone-producing tumours in the digestive system.
Tobacco smoke contains over 70 known carcinogens and is a leading cause of several cancers, including those of the lung, pancreas, and gastrointestinal tract. While NETs are not traditionally classified among smoking-related cancers, some evidence suggests a higher incidence of pulmonary carcinoid tumours in smokers.
Alcohol is also classified as a Group 1 carcinogen. Chronic alcohol use can damage the pancreas and liver, two organs where NETs commonly develop. Although the connection between alcohol consumption and NETs remains less well-established than for other cancers, it may contribute to risk through cumulative cellular damage and inflammation.
Endocrine-disrupting chemicals are substances that interfere with the body’s hormonal systems. Found in plastics (e.g. bisphenol A), pesticides (e.g. DDT), flame retardants, and some cosmetics, EDCs can mimic or block natural hormones and may alter the behaviour of hormone-producing cells.
Given that NETs originate from neuroendocrine cells, there is increasing interest in whether long-term exposure to EDCs could trigger abnormal cell growth or tumour formation. While current evidence is largely limited to animal models or indirect associations, the potential link warrants further investigation.
Exposure to ionising radiation, whether from medical treatment or environmental sources, is a well-known cancer risk factor. Individuals who have undergone radiation therapy for other cancers may have a slightly elevated risk of developing secondary cancers, including NETs.
Environmental radiation—such as that experienced after nuclear accidents or in high-radon areas—may also contribute to long-term cancer risk. Thyroid NETs, though rare, have occasionally been reported following radiation exposure, underscoring the need for cautious use of medical imaging and therapy when possible.
Some medications, including proton pump inhibitors (PPIs) and immunosuppressants, have been examined for potential associations with NET development. PPIs, used to treat acid reflux and gastric ulcers, may cause chronic stimulation of the gastric lining, theoretically increasing the risk of gastric NETs.
However, existing studies have not yet established a clear cause-and-effect relationship. Similarly, other medications such as long-term corticosteroids or hormone replacement therapy may influence endocrine function, but any links to NETs remain speculative at this stage.
Not everyone exposed to carcinogens develops cancer. One reason for this lies in the interaction between environmental risk factors and a person’s genetic makeup.
Individuals with inherited predispositions — such as those with Multiple Endocrine Neoplasia (MEN1), Von Hippel-Lindau (VHL), or Neurofibromatosis Type 1 (NF1) — are more likely to develop NETs, often at a younger age. These genetic conditions increase susceptibility, and environmental exposures may further amplify risk.
Studying environmental carcinogens and NETs presents significant challenges. NETs are less common and often diagnosed late, making it difficult to identify common exposures or causative patterns in large populations. Additionally, the slow-growing nature of many NETs means that exposure could have occurred decades before diagnosis.
Few large-scale epidemiological studies have focused specifically on NETs, and those that exist often rely on self-reported data or lack precise exposure measurements. As a result, most associations between carcinogens and NETs are currently based on indirect evidence, animal studies, or extrapolated from other cancer types.
Nonetheless, growing awareness of NETs and improvements in cancer registries are creating new opportunities for high-quality research that could help clarify environmental risk factors in the future.
While the direct causes of most NETs remain unknown, there are important steps individuals and communities can take to reduce overall cancer risk and promote awareness:
For individuals diagnosed with NETs, understanding potential environmental contributors may offer clarity and support informed discussions with healthcare professionals. While prevention strategies for NETs remain limited, ongoing research and education are crucial steps toward better understanding and reducing risk.
Occupational Benzene Exposure and Risk of Nervous System Cancers
https://www.sciencedirect.com/science/article/pii/S1877782125000396
Current Perspectives on Neuroendocrine Tumors
https://www.sciencedirect.com/science/article/pii/S2949928324000658
Cutting This One Food Could Drastically Reduce Your Cancer Risk
https://www.eatingwell.com/processed-meats-and-cancer-11728821
Associations of Tobacco and Alcohol Use with Risk of Neuroendocrine Tumors
https://aacrjournals.org/cebp/article/28/12/1998/71778/Associations-of-Tobacco-and-Alcohol-Use-with-Risk
Endocrine-Disrupting Chemicals and Cancer
https://www.verywellhealth.com/endocrine-disruptors-and-role-in-cancer-4781570
Risk of Radiation Exposure to Clinical Staff from Paracenteses of Large Volume Ascites After 177Lu-DOTATATE Therapy
https://tech.snmjournals.org/content/50/3/274
Research Reveals Potential Risks of Popular GLP-1 Medications for Some with Neuroendocrine Cancer
https://netrf.org/2024/12/17/research-reveals-potential-risks-of-popular-glp-1-medications-for-some-with-neuroendocrine-cancer/
Hereditary Factors in Neuroendocrine Tumours
https://neuroendocrine.org.au/causes/hereditary/
Clinical and Translational Research Challenges in Neuroendocrine Tumors
https://www.sciencedirect.com/science/article/pii/S0929867320000058
Neuroendocrine Tumors: Challenges and Future Perspectives
https://www.mdpi.com/2077-0383/11/15/4351
