Neuroblastoma - Childhood: Risk Factors

Approved by the Cancer.Net Editorial Board, 09/2023

ON THIS PAGE: You will find out more about the factors that increase the chance of developing neuroblastoma. Use the menu to see other pages.

What are the risk factors for neuroblastoma?

For most types of cancer, a “risk factor” is anything that increases a person’s chance of developing cancer. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do.

For neuroblastoma, the term “risk factor” is more commonly used once a tumor has been found to describe the factors that are used to predict how the tumor will grow and how well treatment will work. Learn more about a tumor's risk grouping in this guide's section on Stages and Risk Groups.

It is known that neuroblastoma occurs more often in boys than in girls. So far, no environmental factors have been shown to increase the risk of developing neuroblastoma.

Rarely, more than 1 member of a family is diagnosed with neuroblastoma. Researchers have found inherited gene mutations, or changes, that play a role in the development of neuroblastoma for children with a family history of the disease. Other genetic changes, called single-nucleotide polymorphisms (SNPs), may contribute to the development of neuroblastoma in children who do not have a family history.

Family history and genetic predisposition

Approximately 1% to 2% of children with neuroblastoma have a family history of the disease. Children with an inherited likelihood of neuroblastoma tend to develop the disease, on average, 9 to 13 months earlier than other children with neuroblastoma. In children who have a family history of neuroblastoma, the disease may occur in both adrenal glands or 2 or more organs.

Neuroblastoma has been diagnosed in people with congenital central hypoventilation syndrome (CCHS), a unique disorder of breathing control associated with Hirschsprung disease (HSCR). CCHS can result from germline mutations, which is a hereditary genetic mutation that is passed down from parent to child, or it may be a new genetic mutation in the child in the paired-like homeobox (PHOX) 2B gene. Mutations in the PHOX2B gene have been found in people with a family history of neuroblastoma and in most cases are associated with HSCR and CCHS. PHOX2B mutations have also been detected occasionally (less than 2% of cases) in DNA samples from neuroblastoma tumors in people with no family history of this disease.

In most people with a family history of neuroblastoma, there are germline mutations in the anaplastic lymphoma kinase (ALK) gene. These genetic mutations result in abnormal ALK activation. Activating ALK mutations have also been identified in DNA from neuroblastoma tumors in children without a family history, and in a subset of patients, ALK amplification is found in neuroblastoma tumors.

Neuroblastoma has also been diagnosed in several people who are missing portions of chromosomes 1p and 11q. These chromosomes are thought to prevent tumor growth.

Genetic factors without a family history

The genetic factors involved in development of neuroblastoma in patients with no family history of the disease are not yet well understood. Although a number of genes with germline mutations that raise the risk of developing neuroblastoma have been identified, including TP53, NRAS, and BRCA2, it is unclear what role they play. Common polymorphisms (including BARD1 or LMO1) have also been identified that have relatively small effects on the risk of a person developing neuroblastoma. In some cases, several polymorphisms can cooperate, leading to a higher risk of neuroblastoma. Research to identify rarer predisposition polymorphisms is ongoing.

Read more about the genetics of cancer. You can also learn more about this topic at the National Institute of Health’s website for the National Human Genome Research Institute (please note this link takes you to a separate website).

The next section in this guide is Symptoms and Signs. It explains what changes or medical problems neuroblastoma can cause. Use the menu to choose a different section to read in this guide.