Do we know what causes non-Hodgkin lymphoma in children?

The exact cause of most cases of childhood non-Hodgkin lymphoma is not known. However, scientists have found that the risk of this cancer is higher with a number of other conditions, which are described in the section, “What are the risk factors for non-Hodgkin lymphoma in children?” Many of these conditions are related to problems with the immune system.

Scientists have found that certain changes in the DNA inside normal lymphocytes can cause them to become lymphoma cells. Normal human cells grow and function based mainly on the information contained in each cell’s chromosomes. Human DNA is packaged in 23 pairs of chromosomes, which are long molecules of DNA in each cell. DNA is the chemical that makes up our genes – the instructions for 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 contain instructions for controlling when our cells grow, divide into new cells, and die. Certain genes that speed up cell growth and division or help cells live longer are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

For example, translocations are a type of DNA change that can cause non-Hodgkin lymphoma to develop. A translocation means that DNA from one chromosome breaks off and attaches to a different chromosome. When this happens, oncogenes can be turned on or tumor suppressor genes can be turned off.

Some people inherit DNA mutations from a parent that increase their risk for some types of cancer. But non-Hodgkin lymphoma is not one of the cancer types often caused by these inherited mutations.

Usually, DNA mutations related to non-Hodgkin lymphoma occur during life rather than having been inherited before birth. In rare cases, these acquired mutations may result from exposure to radiation or other factors. But often they occur for no apparent reason.

The combination of immune deficiencies (from inherited conditions, drug treatment, or HIV infection) and Epstein-Barr virus (EBV) infection can cause some types of non-Hodgkin lymphoma. EBV is a virus that infects B lymphocytes. It can cause the cells to grow and divide and extend their lifespan. In young adults infected with EBV, it often causes infectious mononucleosis, also known as mono. Mono is usually not a serious disease because the person's T cells destroy the B cells that are infected with EBV. But when children have an immune deficiency, EBV-infected B cells may grow and accumulate. These cells have an increased risk for developing DNA changes. If these changes affect certain oncogenes or tumor suppressor genes, lymphoma may develop.

Scientists have learned a lot about the gene changes commonly seen in lymphoma cells. This is being used to develop more accurate tests for detecting and classifying certain types of non-Hodgkin lymphoma. Some of these discoveries are being used to develop new treatments as well.

Most children who develop non-Hodgkin lymphoma 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 do not know what causes them in children without these risk factors.