Neuroblastoma - Childhood: Risk Factors

Approved by the Cancer.Net Editorial Board, 03/2015

ON THIS PAGE: You will find out more about the factors that increase the chance of developing this type of tumor. To see other pages, use the menu on the side of your screen

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, nine to thirteen months earlier than other children with neuroblastoma. In children who have a family history of neuroblastoma, the disease may occur in two 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 mutation passed directly from parent to child, in the paired-like homeobox (PHOX) 2B gene. Germline PHOX2B alterations are present in the tumors of people with neuroblastoma and with CCHS and/or HSCR. Rare germline PHOX2B mutations have also been found in patients who are genetically predisposed to neuroblastoma.

Most of the time, when multiple members of a family have neuroblastoma, they have germline mutations in the anaplastic lymphoma kinase (ALK) gene. These mutations can be found in a blood sample. However, ALK mutations have also been found in DNA from tumors in some patients without a family history.

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. Common copy number variation of NBPF23 has been shown to be associated with neuroblastoma. This involves looking at the genes and how they differ between individuals. In addition, genome-wide association studies have identified a number of germline neuroblastoma susceptibility SNPs. These include SNPs within or upstream of these genes:

  • CASC15

  • CASC14

  • BARD1

  • LMO1

  • DUSP12

  • HSD17B12

  • DDX4/IL31RA

  • HACE1

  • LIN28B genes

  • Rare variants in TP53

  • NEFL 

However, these variants account for only a small portion of the risk for developing neuroblastoma. Read more about the genetics of cancer. Learn more about genetic studies here (please note this link takes you out of Cancer.Net). 

The next section in this guide is Symptoms and Signs and it explains what body changes or medical problems this disease can cause. Or, use the menu on the side of your screen to choose another section to continue reading this guide.