Neuroblastoma - Childhood: Risk Factors

Approved by the Cancer.Net Editorial Board, 04/2018

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.

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 to describe the factors that are used to predict how the tumor will grow and how well treatment will work (see Stages and Groups).

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 one member of a family is diagnosed with neuroblastoma.

Researchers have found inherited gene mutations (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 thirteen months earlier than other children with neuroblastoma. In children who have a family history of neuroblastoma, the disease may occur in 2 or more organs.

Neuroblastoma tumors have been diagnosed in patients with congenital central hypoventilation syndrome (CCHS), a unique disorder of breathing control associated with Hirschsprung disease (HSCR). CCHS results from germline mutations, which is a genetic mutation that may be passed directly from parent to child or may be a new genetic mutation in the child, in the paired-like homeobox (PHOX) 2B gene. Mutations in the PHOX2B homeobox gene have also been found in patients with a family history of neuroblastoma, and in most cases are associated with HSCR and CCHS. PHOX2B mutations have also been detected rarely (< 2%) in DNA samples from neuroblastoma tumors in patients without any family history.

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

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

Genetic factors without a family history

The genetic factors that have a role in the development of neuroblastoma in patients who do not have a family history are not well understood. Although a number of germline genes with damaging mutations that can predispose a person to 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 developing neuroblastoma. In some cases, several polymorphisms can cooperate, leading to a higher risk of neuroblastoma. Research to identify more rare predisposition polymorphisms is ongoing.

Read more about the genetics of cancer. 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 body changes or medical problems childhood neuroblastoma can cause. Use the menu to choose a different section to read in this guide.