Causes and Risk Factors of Non-Hodgkin Lymphoma

Illustration of the Epstein barr virus

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Before reading about the causes of non-Hodgkin lymphoma, or NHL, it is important to know that there are many different types of NHL.

They are all malignancies of white blood cells (lymphocytes), but in many cases, the subtypes of NHL differ in their symptoms, prognoses, and the type of lymphocytes involved. Important causes of NHL are also likely to differ depending on the specific NHL subtype in question.

That said, scientists who study lymphoma still find it useful to talk about various potential causes of NHL. The takeaway point is that, if something is called a “risk factor for NHL,” or “associated with NHL,” that doesn't mean it’s a risk factor for all of the different types of NHL.

The Microbial Connection

Like Hodgkin’s lymphoma, NHL has been linked to a number of infections:

  • Epstein-Barr virus, or EBV, is linked to Burkitt lymphoma, the most common NHL in children and adolescents around the world.
  • Patients with HIV are predisposed to a variety of non-Hodgkin lymphomas. Burkitt lymphoma and diffuse large B-cell lymphoma are two of the most common HIV-associated lymphomas.
  • When Burkitt lymphoma is associated with HIV, some 30% to 50% of patients are also EBV-positive. A defective immune response against EBV in HIV-positive individuals is thought to contribute to Burkitt lymphoma.
  • Human T-cell lymphotropic virus type-1, or HTLV-1, is very rare in North America, but it is endemic to areas of Japan, Africa, and the Caribbean. HTLV-1 causes adult T-cell leukemia-lymphoma, which is an NHL of the T-lymphocytes.
  • Helicobacter pylori, a bacterium that is associated with ulcers in the stomach, may also cause certain non-Hodgkin lymphomas of the gastrointestinal tract.
  • Chronic hepatitis C infection is associated with B-cell non-Hodgkin lymphomas.

Weakened Immune System

Lymphoma is a cancer of the lymphocytes, which are key players in the human immune system. Conditions that weaken the immune system can increase the risk of many different types of cancers, including NHL:

  • HIV weakens the immune system. There is a clear link between declining CD4 lymphocyte counts and the risk of developing NHL.
  • Patients who get organ transplantation need to take drugs that suppress the immune system. This also seems to increase the chances of lymphoma.
  • Some inherited diseases affecting the immune system (e.g., ataxia telangiectasia) can increase the risk of lymphoma.

Chemicals and Exposures

Rates for new cases of NHL doubled from the 1960s to the 1990s, leading people to wonder about the possible causes. It’s a question that has driven a lot of research, including investigation of pesticides.

Pesticides have been suggested as a cause of NHL, but the evidence has been inconsistent. Only a few studies of pesticides have been large enough to evaluate the potential link between NHL subtypes and specific pesticide exposures.

Studies of survivors of atomic bombs and nuclear reactor accidents have shown they have an increased risk of developing several types of malignancies, including non-Hodgkin lymphoma.

Previous Treatment for Other Cancers

Individuals who have received chemotherapy or radiation therapy for previous cancers have a slightly greater chance of developing non-Hodgkin lymphoma later in life.

Age and Sex

When researchers crunch numbers, they find that the chance of getting NHL increases as you get older. It is also more common in men than in women.

A Word From Verywell

The different types of NHL are all malignancies of lymphocytes, but they can vary significantly in disease course and prognosis—and may differ in important ways with respect to causes and risk factors.

For some types of NHL, the genetic and environmental underpinnings of the disease are starting to be better understood, and links have been found to certain infections and responses by the immune system.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Indranil Mallick, MD
 Indranil Mallick, MD, DNB, is a radiation oncologist with a special interest in lymphoma.