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The exact cause of most cases of childhood non-Hodgkin lymphoma (NHL) is not known. However, scientists have found that the risk of this cancer is higher if a child or teen has any of the conditions described in Risk Factors for Non-Hodgkin Lymphoma in Children. Many of these conditions are related to problems with the immune system.

Lymphoma is a cancer that starts in cells called lymphocytes, which are a type of white blood cell. Scientists have found that certain changes in the DNA inside normal lymphocytes can make them become lymphoma cells. DNA is the chemical in our cells that makes up our genes, which control how our cells function. We look like our parents because they are the source of our DNA. But our genes affect more than the way we look.

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

• Genes that normally help cells grow, divide, and stay alive can sometimes change to become oncogenes.
• Genes that help keep cell division under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA mutations (changes) that create oncogenes, or that turn off tumor suppressor genes.

Inherited versus acquired gene changes

Some people inherit DNA changes from a parent that increase their risk for certain types of cancer. For example, some children inherit DNA changes that result in them having a weakened immune system, which can increase their risk for NHL. But this is not common.

More often, DNA changes related to NHL occur during life rather than having been inherited before birth. In some cases, these acquired changes result from an outside exposure to radiation or other factors, such as treatment for another condition that results in a weakened immune system. But in many cases, acquired gene changes seem to occur randomly, without having an outside cause.

The combination of immune deficiencies (from inherited conditions, medical treatment, or HIV infection) and Epstein-Barr virus (EBV) infection can cause some types of NHL. EBV infects B lymphocytes. It can make the cells grow, divide, and live longer than they should. In young adults, EBV often causes infectious mononucleosis, also known as mono. Mono is usually not a serious disease because the person’s immune system destroys the B cells that are infected with EBV. But when a child has an immune deficiency, EBV-infected B cells may grow and build up. These cells have an increased risk for DNA changes. If these changes affect certain oncogenes or tumor suppressor genes, lymphoma may develop.

Most children and teens who develop NHL in the United States do not have an immune deficiency or evidence of EBV infection. Even though researchers have found many of the key DNA changes in lymphoma cells, they still don't know what causes them in children and teens who don't have these risk factors.