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 increased 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 made great progress in understanding how certain changes in DNA can cause normal lymphocytes 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 resemble 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 and divide. Certain genes that promote cell growth and division into new cells 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 (defects) that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA mutations from a parent that increase their risk for 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.

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 becomes attached to a different chromosome. When this happens, oncogenes can be turned on or tumor suppressor genes can be turned off.

The combination of immune deficiencies (due to 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, causing the cells to grow and divide and extending their lifespan. In most young adults, it 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 a T-cell deficiency (which may be present at birth or caused by HIV infection or by certain drugs that decrease their function), the EBV-infected B cells may grow and accumulate. These growing cells have an increased risk for developing DNA mutations or chromosome translocations. If these changes affect certain oncogenes or tumor suppressor genes, lymphoma may develop.

Scientists have learned a lot about the exact genes involved in this process and how they may cause lymphoma. This information is being used to develop new and more accurate tests for detecting and classifying certain types of non-Hodgkin lymphoma. It is hoped that these discoveries will soon be applied to developing new treatments as well.

Even though researchers have described many of the key DNA changes in lymphoma cells and are beginning to understand how they develop in people with certain risk factors, they still do not know why most lymphomas develop in children who have no apparent risk factors.

Last Medical Review: 07/08/2009
Last Revised: 07/08/2009