Causes and Risk Factors of Neuroblastoma

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Neuroblastoma is caused by the mutation of immature nerve cells.

While experts aren't exactly sure what causes these nerve cells to mutate, studies have shown that the corruption of certain genes or inherited risk factors can increase the chance of diagnosis.

For example, changes to the ALK gene, or a family history of neuroblastoma, have been identified as reasons why a person may develop cancer.

In greater detail, this article will review some of the known risk factors associated with neuroblastoma.

Neuroblastoma Risk Factors - Illustration by Mira Norian

Verywell / Mira Norian

Common Causes

The tumor develops from immature nerve cells and typically forms in the adrenal glands (around the kidneys). However, cancer could also grow in the neck, chest, back, pelvis, and spinal cord.

Sometimes the only noticeable symptom is a lump that can be felt under the skin, while other times, people may experience severe illness.

The reason immature nerve cells sometimes turn into neuroblastoma isn’t understood. Researchers believe it’s related to mutations in specific genes, but it is not known what causes these genes to mutate in some people.


Normally as infants grow, their nerve cells continue to develop and mature. Genes are responsible for controlling cell growth and killing cells when they reach the end of their normal life cycle.

Sometimes a mutation can happen in genes, which causes cells to divide and grow rapidly while also turning off the gene that naturally suppresses tumors. This means cells grow out of control with no way for them to stop growing naturally.

Researchers have been able to identify some of the genes that play a role in neuroblastoma development:

  • ALK gene: Changes to the ALK gene may account for about 15% of neuroblastoma cases. Researchers believe the ALK gene plays a role in the growth and development of nerve cells. It’s thought this gene is passed through families.
  • PHOX2B gene: This gene plays a role in helping immature nerve cells develop into healthy mature nerve cells. Mutations in the PHOX2B gene are believed to be a common hereditary (passed through families) cause of neuroblastoma.
  • MYCN oncogene: Sometimes neuroblastoma cells carry extra copies of the MYCN oncogene. Carrying extra copies of a gene is often called an amplified gene. This genetic mutation is sometimes a sign the tumor will grow more rapidly, which may make it more difficult to treat. The MYCN oncogene is believed to account for up to 25% of high-risk cases.
  • ATRX gene: The ATRX gene mutation is more likely to be present in children who are diagnosed with neuroblastoma at an older age. Research suggests these types of tumors grow more slowly, although they could be harder to treat.
  • NTRK1 gene: Tumors with the NTRK1 gene tend to appear in younger children and have a lower cancer stage. Research suggests NTRK1 tumors tend to have a better outlook for treatment and a better prognosis.

Risk Factors

There are no known lifestyle or environmental risk factors that cause neuroblastoma. This may be because of the young age at which the cancer tends to develop. The known risk factors for neuroblastoma are out of your control and include:

  • Age: Neuroblastoma is more common in young children and infants. Most cases occur in children under the age of 5, and it’s very rare to be diagnosed with neuroblastoma over the age of 10.
  • Family history: In most cases, neuroblastoma doesn’t appear to be a hereditary condition, meaning it usually doesn’t run in families. About 1% to 2% of neuroblastoma cases are familial, meaning they affect more than one member of the family.
  • History of birth defects: Children and infants with nonchromosomal birth defects, such as congenital heart disease and nervous system defects, may have a higher risk of developing childhood cancers. Research suggests the number of major birth defects diagnosed is directly related to an increase in risk for childhood cancer.

A Word From Verywell

Receiving a cancer diagnosis can be scary, especially if it’s your child. While it’s frustrating not to understand the exact cause of the disease, new research continues to help better understand the cause of cancer.

Currently, genetic mutations are the only known possible causes for neuroblastoma. It’s important to remember these mutations are rare and are never anyone’s fault. 

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mahapatra S, Challagundla KB. Neuroblastoma. In: StatPearls. StatPearls Publishing; 2021.

  2. Barr EK, Applebaum MA. Genetic predisposition to neuroblastoma. Children (Basel). 2018;5(9):119. doi: 10.3390/children5090119

  3. Zeineldin M, Federico S, Chen X, et al. MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nat Commun. 2020;11:913. doi: 10.1038/s41467-020-14682-6

  4. Light JE, Koyama H, Minturn JE, et al. Clinical significance of NTRK family gene expression in neuroblastomas. Pediatr Blood Cancer. 2012;59(2):226-232. doi: 10.1002/pbc.23343

  5. Lupo PJ, Schraw JM, Desrosiers TA, et al. Association between birth defects and cancer risk among children and adolescents in a population-based assessment of 10 million live births. JAMA Oncol. 2019;5(8):1-10. doi: 10.1001/jamaoncol.2019.1215

By Ashley Braun, MPH, RD
Ashley Braun, MPH, RD, is a registered dietitian and public health professional with over 5 years of experience educating people on health-related topics using evidence-based information. Her experience includes educating on a wide range of conditions, including diabetes, heart disease, HIV, neurological conditions, and more.