What Causes Non-Hodgkin Lymphoma in Children?

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 the child 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 help cells grow, divide, and stay alive are called oncogenes.
  • Genes that slow down cell division or make cells die at the right time are called tumor suppressor genes.

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 NHL to develop. A translocation means that part of one chromosome (a long strand of DNA) 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 changes from a parent that increase their risk for some types of cancer. But NHL is not one of the cancer types often caused by these inherited mutations.

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

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.

Scientists have learned a lot about the gene changes commonly seen in lymphoma cells. This is being used to develop better tests to detect and classify certain types of NHL. Some of these discoveries are being used to create new treatments as well.

Most children 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 without these risk factors.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Allen CE, Kamdar KY, Bollard CM, Gross TG. Malignant non-Hodgkin lymphomas in children. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 7th ed. Philadelphia Pa: Lippincott Williams & Wilkins; 2016:587–603.

Kamdar KY, Sandlund JT, Bollard CM. Malignant lymphomas in childhood. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa: Elsevier; 2013:1255−1266.

Rabin KR, Margolin JF, Kamdar KY, Poplack DG. Leukemias and lymphomas of childhood. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015:1500–1510.


Last Revised: January 27, 2016

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