What Causes Non-Hodgkin Lymphoma?

Researchers have found that non-Hodgkin lymphoma (NHL) is linked with a number of risk factors, but the cause of most lymphomas is not known. This is complicated by the fact that lymphomas are actually a diverse group of cancers.

Still, scientists have made a lot of progress in understanding how certain changes in DNA can cause normal lymphocytes to 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 DNA affects more than just how we look. 

Some genes control when cells grow, divide, and die:

  • Genes that help cells grow, divide, and stay alive are called oncogenes
  • Genes that help keep cell division under control 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.

Some people inherit DNA mutations 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. In other words, having a family history of lymphoma does not seem to increase your risk of lymphoma.

Gene changes related to NHL are usually acquired during life, rather than being inherited. Acquired gene changes can result from exposure to radiation, cancer-causing chemicals, or infections, but often these changes occur for no apparent reason. They seem to happen more often as we age, which might help explain why most lymphomas are seen in older people.

For some types of lymphoma, some of the gene changes that led to the lymphoma are now known. For example, in follicular lymphoma, the cells often have an exchange of DNA (known as a translocation) between chromosomes 14 and 18, which turns on the BCL-2 oncogene. (Chromosomes are long strands of DNA in each cell.) This oncogene stops the cell from dying at the right time, which can lead to lymphoma. 

Scientists are learning much about the exact gene changes involved in the different types of NHL. This information is being used to develop more accurate tests to detect and classify certain types of lymphoma. Hopefully, these discoveries can be used to develop new treatments as well.

While researchers are beginning to understand some of the gene changes that can lead to NHL, they still do not know why many of these gene changes develop, especially in people with no apparent risk factors.

Lymphocytes (the cells from which lymphomas start) are immune system cells, so it’s not surprising that changes in the immune system seem to play an important role in many cases of lymphoma:

  • People with immune deficiencies (due to inherited conditions, treatment with certain drugs, organ transplants, or HIV infection) have a much higher chance of developing lymphoma than people without a weakened immune system.
  • People with certain autoimmune diseases (where the immune system constantly attacks a certain part of the body) have an increased risk of lymphoma.
  • People with certain chronic infections are also at increased risk, probably because the immune system is constantly making new lymphocytes to fight the infection, which increases the chances for mistakes in their DNA.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. 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.

Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.

Last Medical Review: May 31, 2016 Last Revised: May 31, 2016

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