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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 there are many types of lymphomas are actually a diverse group of cancers, which might have different causes.

Changes in genes

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 our genes affect more than just how we look.

Some genes normally help control when our cells grow, divide to make new cells, or repair mistakes in DNA, or they cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control. For example:

  • Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
  • Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
  • Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Some people inherit DNA mutations from a parent that increase their risk for some types of cancer. Having a family history of lymphoma does seem to increase your risk of lymphoma. Still, most people with lymphoma don’t have a strong family history of it.

Gene changes related to NHL are usually acquired (picked up) 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 clear reason. They seem to happen more often as we age, which might help explain why most lymphomas are seen in older people.

Some of the gene changes that lead to certain types of 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 about the exact gene changes involved in the different types of NHL. This information is being used to develop better 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 clear risk factors.

Changes in the immune system

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 weakened immune systems (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 oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

Freedman AS, Freidberg JW, Aster JC. Clinical presentation and initial evaluation of non-Hodgkin lymphoma. In: Post T, ed. Uptodate. UpToDate; 2022. Accessed September 13, 2023.

Luo J, Craver A, Bahl K, et al. Etiology of non-Hodgkin lymphoma: A review from epidemiologic studies. J Natl Cancer Cent. 2022.


Last Revised: February 15, 2024

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