Causes, Risk Factors, and Prevention of Neuroblastoma

Neuroblastoma is the most common cancer in infants and most often occurs in children under the age of 5. While there are a few known genetic factors that increase the risk of neuroblastoma, the cause of most neuroblastomas is not known.

What causes neuroblastoma?

Scientists have found some risk factors, but most children with neuroblastoma do not have any known risk factors. A risk factor is anything that affects a person’s chance of getting a disease such as cancer.

How normal cells become neuroblastoma cells

Nerve cells and cells in the medulla (center) of the adrenal gland start out as neuroblasts in a growing fetus. Most often, neuroblasts grow and develop into mature cells. Neuroblastomas can occur when normal fetal neuroblasts do not mature but instead continue to grow and divide.

Some neuroblasts might not have matured completely by the time a baby is born. Most of these eventually mature into normal nerve cells over time, or they simply die off and do not form cancer.

But sometimes, neuroblasts do not mature and continue to grow, forming a tumor. Many of these tumors will still eventually mature into nerve tissue or go away on their own. But as children get older, it becomes less likely that these cells will mature, and more likely that they will grow into cancer.

Why some neuroblasts do not mature

The reason some neuroblasts do not mature is because they have changes in their DNA. DNA is the chemical in each of our cells that makes up our genes. Genes control how our cells function. Changes (mutations) in the DNA inside our cells can sometimes change the way some genes work, which can promote cancer growth.

Some genes control when our cells grow, divide into new cells, and die:

• Genes that help cells grow, divide, or stay alive can lose the ability to turn off and are called oncogenes.
• Genes that tell cells to stop dividing or cause cells to die at the right time are called tumor suppressor genes.
• DNA repair genes find and fix DNA damage that happens during cell growth or from the environment.

Neuroblastoma cells can have chromosome changes (such as having too many or too few chromosomes, or missing part of a chromosome) that affect certain genes. Scientists are still trying to determine which genes are affected by these chromosome changes, and how these changes affect the growth of neuroblastoma.

Acquired versus inherited gene changes in neuroblastoma

Most neuroblastomas are the result of gene changes in neuroblasts that happen during the child’s development, sometimes even before birth. The cause of these acquired (somatic) gene changes is not known.

These acquired gene changes are found only in the child’s cancer cells, so they will not be passed on to their children.

In rare cases, neuroblastoma occurs because of gene changes inherited from a parent. Inherited (germline) changes in certain genes account for most hereditary (familial) neuroblastomas:

• Changes in the ALK oncogene account for most cases of inherited neuroblastoma.
• Changes in PHOX2B, a gene that normally helps nerve cells mature, account for a small number of inherited neuroblastomas.

It is still not clear what causes many of the gene and chromosome changes that can lead to neuroblastoma. There are no clear lifestyle-related or environmental causes of neuroblastomas. Researchers have not found anything that can be done to prevent these cancers.

Risk factors for neuroblastoma

A risk factor is anything that increases the chances of getting a disease such as cancer. Different types of cancer have different risk factors.

Can neuroblastoma be prevented?

Currently, there are no known ways to prevent most cancers in children.

The known risk factors for neuroblastoma cannot be changed. Some studies suggest prenatal multi-vitamins or folic acid during pregnancy might lower the risk of neuroblastoma. Further research is needed.

If there is a history of neuroblastoma in your family, you may want to talk with a genetic counselor about your child’s risk of developing the disease. It is important to remember, though, that familial neuroblastoma is very rare.