The exact cause of most cases of non-Hodgkin lymphoma is not known. However, scientists have found that this cancer is associated with a number of other conditions, some of which are described in the section on risk factors. Most children with non-Hodgkin lymphoma do not have any known risk factors, and the causes of their cancers remain unknown at this time.

In addition to the immunodeficiency patterns mentioned in the section "What Are the Risk Factors for Childhood Non-Hodgkin Lymphoma?", an increased incidence of non-Hodgkin lymphoma has been found in children with congenital immunodeficiency syndromes, including:

• Wiskott-Aldrich syndrome
• Severe combined immunodeficiency syndrome (SCID)
• Ataxia-telangiectasia
• Common variable immunodeficiency
• Bloom syndrome
• X-linked lymphoproliferative syndrome

This suggests that immune system problems can make a person more likely to develop non-Hodgkin lymphoma.

During the past few years, scientists have made great progress in understanding how certain changes in DNA can cause normal lymphocytes to become lymphomas. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance.

Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the appropriate time are called tumor suppressor genes. Cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Some people with certain types of cancer have DNA mutations they inherited from a parent. These changes increase their risk for the disease. 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. These acquired mutations may result from exposure to radiation or cancer-causing chemicals. But sometimes they occur for no apparent reason.

Every time a cell prepares to divide into 2 new cells, it must duplicate its DNA. This process is not perfect, and copying errors sometimes occur. Fortunately, cells have repair enzymes that proofread DNA. However, some errors may slip past, especially if the cells are growing rapidly.

Translocations are another type of DNA abnormality involved in some cases of non-Hodgkin lymphoma. Human DNA is packaged in 23 pairs of chromosomes. A translocation means that DNA from one chromosome becomes attached to a different chromosome. Translocations can cause oncogenes to be turned on and often occur in cases of non-Hodgkin lymphoma.

The combination of immune deficiencies (due to inherited conditions, drug treatment, or HIV infection) and Epstein-Barr virus (EBV) infection can cause non-Hodgkin lymphoma to develop. EBV is a virus that infects B lymphocytes, causing them to grow and divide and extending their lifespan. In most people, it causes infectious mononucleosis, also known as "mono." Mono is usually not a serious disease because the patient’s T cells destroy B cells infected with EBV. But when people have a T-cell deficiency (which may be present at birth, secondary to HIV infection, or caused by drugs that decrease their function such as after a transplant), the EBV-infected B cells grow and accumulate. These growing cells have an increased risk for developing DNA mutations or gene translocations. If these changes affect certain oncogenes or tumor suppressor genes, lymphoma will develop.

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

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 people with no apparent risk factors.

Revised: 03/08/2007