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Lymphoma Causes and Risk Factors

Medically reviewed by Leonora Valdez Rojas, M.D.
Written by Kelly Crumrin
Updated on November 19, 2024

Lymphoma is a type of blood cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. When lymphocytes develop genetic mutations (DNA changes), they can start to grow too quickly and live longer than healthy cells. This abnormal growth can lead to cancer. Different factors might increase the risk of lymphoma, including infections, lifestyle choices, genetic disorders, and immune system problems.

The two main types of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL includes many subtypes, each with specific characteristics and treatments.

How Does Lymphoma Usually Start?

Like other cancers, lymphoma develops because of genetic mutations (also called pathogenic variants, or changes), which cause cells to divide and grow in an uncontrolled way. There are two main types of genetic variants — inherited and acquired.

Acquired variants:

  • Develop throughout a person’s life
  • Can be triggered by aging and exposure to carcinogens (cancer-causing substances), such as radiation, certain chemicals, smoking, and some viruses
  • Are found only in the DNA of certain cells

Inherited variants:

  • Are passed down from parents to their children
  • Are already in the DNA of all cells at birth
  • Occur far less commonly than acquired variants

Both acquired and inherited variants are thought to raise the risk of developing Hodgkin and non-Hodgkin lymphoma. However, doctors still don’t fully understand why some people get lymphoma and others don’t.

How Cells Transform Into Cancer

Normal cells divide in an organized way to replace old or damaged cells. Certain genes in each cell control when cells should start and stop dividing. Some genes also check for mistakes in the cell’s DNA and either fix them or tell the cell to self-destruct if the DNA is too damaged.

If a genetic mutation causes one or more of these genes to stop working correctly, the cells can divide faster and more chaotically, causing further abnormalities. Mutations can build up, making the cells grow even faster and become more disordered. If these cells spread into nearby tissue or break off and move to other parts of the body, they have become cancerous.

Risk Factors for Lymphoma

It’s important to know that although science is good at finding correlations (connections) between factors and disease, these links don’t mean that one causes the other. Many risk factors for lymphoma have been identified and are being studied to better understand how they might contribute to the disease.

Since genetic variants cause lymphoma, risk factors include anything that can encourage those changes to happen. Risk factors vary by the type of lymphoma. Hodgkin lymphoma and NHL share some risk factors, and others are more strongly linked — or only linked — to Hodgkin lymphoma, NHL, or specific subtypes of NHL.

Inherited Factors

Genes passed down from parents may raise the risk of Hodgkin lymphoma. Having a first-degree relative (parent or sibling) with lymphoma may also make you more likely to develop either Hodgkin or non-Hodgkin lymphoma.

Some rare inherited conditions that weaken the immune system may increase lymphoma risk. These include:

  • Wiskott-Aldrich syndrome
  • Klinefelter’s syndrome
  • Ataxia-telangiectasia

Sex, Gender, and Ethnicity

Overall, men have a higher risk of developing lymphoma than women, according to a study in the American Journal of Hematology. Follicular lymphoma occurs more commonly in women. Certain rare types of lymphoma are specific to one sex, such as primary testicular lymphoma in men and primary breast lymphoma in women, according to the American Cancer Society.

In the United States, white people are more likely to have NHL than African Americans or Asian Americans, per the American Cancer Society.

Age

Mutations in DNA are inevitable, building up with age. Researchers believe that tens of thousands of mutations may accumulate by the time a person turns 60. However, only a small percentage of people will develop cancer.

Both Hodgkin and non-Hodgkin lymphoma can develop at any age, from childhood through older adulthood. However, NHL becomes more common with age, with most diagnoses made in people in their 60s and older.

Hodgkin lymphoma is most common in two age groups — young adults in their 20s and adults 55 or older. Most Hodgkin lymphoma cases are diagnosed between ages 15 and 34.

Environmental Factors

Anything that raises the risk of acquired genetic mutations also raises the risk of lymphoma and other types of cancer. Many risk factors for lymphoma involve problems with the immune system.

Geography

Non-Hodgkin lymphoma occurs more commonly in developed countries, including the United States and nations in Europe. Researchers aren’t sure why this is, but one idea is that certain infections related to lymphoma might be more widespread in these countries.

Infections

Certain infections from viruses and bacteria have been shown to raise the risk of lymphoma.

  • Epstein-Barr virus, which causes mononucleosis, is found in about 30 percent of Hodgkin lymphoma cells. Epstein-Barr virus may also increase the risk of NHL subtypes, including Burkitt lymphoma and natural killer/T-cell lymphoma.
  • Human immunodeficiency virus (HIV) raises the risk of developing various types of lymphoma.
  • Human T-cell lymphotropic virus type 1 is linked with a higher risk of some lymphomas.
  • Helicobacter pylori, a bacteria that causes stomach ulcers, is linked to mantle cell lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (affecting the stomach).
  • Hepatitis B virus raises the risk of NHL, specifically B-cell NHL, by 2.5 times.
  • Hepatitis C, which is caused by a virus, is linked with splenic marginal zone lymphoma and developing diffuse large B-cell lymphoma (DLBCL), a subtype of NHL.
  • Human herpes virus 8 is linked with a rare type of NHL called primary effusion lymphoma, especially in people with HIV.
  • Borrelia burgdorferi, a bacteria that causes Lyme disease, is associated with cutaneous (skin-related) MALT lymphoma and can cause itchy skin.
  • Chlamydophila psittaci, a type of bacteria, is associated with ocular MALT lymphoma, which affects the eyes.
  • Coxiella burnetii, a type of bacteria, is linked to several types of NHL, including DLBCL.

Bacterial infections often cause chronic inflammation, which can trigger cell mutations leading to lymphoma.

Autoimmune Conditions

Certain autoimmune health conditions are associated with an increased risk of developing NHL. Researchers haven’t yet established whether this increased risk is due to inflammation caused by the condition itself or to side effects of treatment. Medications for autoimmune conditions generally work by suppressing aspects of the immune system.

Autoimmune conditions associated with a higher risk for NHL include:

  • Rheumatoid arthritis — This condition causes pain, swelling, and damage to the joints.
  • Systemic lupus erythematosus (also known simply as lupus) — Can attack the skin, kidneys, central nervous system, and other tissues.
  • Sjögren’s syndrome — May cause dry eyes, dry mouth, and other symptoms.
  • Celiac disease — Eating gluten causes damage to the small intestine and is linked to certain rare cancers like peripheral T-cell lymphomas.
  • Hashimoto’s thyroiditis — This condition affects the thyroid and is linked with a higher risk of DLBCL and other forms of NHL.

Read more about conditions related to lymphoma.

Other Health Conditions

Recipients of organ transplants have a higher risk of non-Hodgkin lymphoma, possibly due to the medications they must take to prevent rejection. People who’ve been treated for Hodgkin lymphoma have a higher risk of developing NHL later on, either due to their treatments or to Hodgkin lymphoma itself.

Medications

Some chemotherapy drugs used to treat cancer may increase the risk of developing NHL. Certain medications used to treat autoimmune conditions, including methotrexate (sold as brands such as Otrexup, Rasuvo, Rheumatrex, Trexall, and Xatmep) and tumor necrosis factor inhibitors such as infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia), may be associated with an increased risk of NHL. More studies are needed to better understand these links.

Some studies suggest that Janus kinase (JAK) inhibitors, like tofacitinib (Xeljanz), may increase lymphoma risk in certain high-risk groups, such as people with cardiovascular disease (heart and blood vessel conditions). However, more research is needed to understand this possible risk. JAK inhibitors are used to treat arthritis and other inflammatory diseases.

People who use oral contraceptives may have a lower risk of NHL than those who do not.

Radiation

Exposure to high levels of ionizing radiation increases the risk of NHL. Sources of ionizing radiation include:

  • Radiation therapy
  • Building materials
  • Nuclear medicine procedures
  • Medical imaging, such as X-rays, computed tomography, positron emission tomography, and fluoroscopy (a live X-ray video of the body)

Chemicals

Some chemicals are linked to a higher risk of lymphoma, especially herbicides and pesticides. These include:

  • Organochlorine
  • Organophosphate
  • Phenoxy acid compounds
  • Glyphosate (found in products such as Roundup)

Exposure to benzene, a common chemical used in plastics, rubber, dye, detergents, and gasoline, is known to cause cancer in general and may be linked to NHL. Cigarette smoke, including secondhand smoke, contains this chemical and accounts for about half of benzene exposure for people in the U.S.

Occupational Risk

Non-Hodgkin lymphoma occurs more commonly in agricultural communities, and farm workers tend to develop certain subtypes at a higher rate than people in other occupations. People who work as hairdressers or in the textile industry may also have a higher risk of developing NHL. These jobs and some related hobbies may increase exposure to cancer-causing chemicals, like those listed above.

Obesity

Obesity is defined as having a body mass index of 30 or higher. Obesity increases the risk of DLBCL and is linked with a 17 percent increased risk of developing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), another subtype of NHL.

Acquired Mutations Associated With Lymphoma

Scientists have identified many acquired genetic mutations in lymphocytes that can lead to lymphoma. Genetic testing of lymphoma cells is often part of the diagnostic process because it helps doctors tell the different types of lymphoma apart. Understanding which mutations are in the cancer cells also helps doctors recommend effective treatment options.

Read more about specific genetic mutations commonly associated with different types of lymphoma.

Can Lymphoma Be Prevented?

There’s no certain way to prevent lymphoma. Many people who develop lymphoma have no known risk factors. Most risk factors, including age, genetics, and ethnicity, can’t be controlled. If you’re concerned about your risk, you can take steps like the following to address environmental factors:

  • Limit exposure to radiation and harmful chemicals. If you work with these substances, use protective equipment and follow all safety guidelines.
  • Follow general cancer prevention strategies. Eat a healthy diet — get plenty of fruits, vegetables, and whole grains, and limit red and processed meats — which can also help you maintain a healthy weight.
  • Quit smoking and avoid secondhand smoke.

If your doctor has told you that you have risk factors for lymphoma, make sure to attend all follow-up appointments for monitoring tests. You may not notice symptoms right away, and early detection may mean additional treatment options and improved outcomes.

Talk to Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their caregivers. On MyLymphomaTeam, more than 20,000 members come together to ask questions, give advice, and share their experiences with others who understand life with different forms of lymphoma.

Have you been diagnosed with a type of lymphoma? Do you have more questions about the causes and risk factors? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Understanding Lymphoma — Lymphoma Research Foundation
  2. Pathogenic Variant — National Cancer Institute
  3. Hodgkin Lymphoma Risk Factors — American Cancer Society
  4. Non-Hodgkin Lymphoma Risk Factors — American Cancer Society
  5. Cell Division and Cancer — Nature Education
  6. What Is Cancer? — National Cancer Institute
  7. Follicular Lymphoma: A Review of Mechanisms, Risk Factors, and Unmet Needs — AJMC
  8. Aging and the Rise of Somatic Cancer-Associated Mutations in Normal Tissues — PLOS Genetics
  9. Lymphoma — Yale Medicine
  10. Hodgkin Lymphoma — Leukemia & Lymphoma Society
  11. Genetic Predisposition to Lymphomas: Overview of Rare Syndromes and Inherited Familial Variants — Mutation Research/Reviews in Mutation Research
  12. Sex Differences in Lymphoma Incidence and Mortality by Subtype: A Population-Based Study — American Journal of Hematology
  13. What Is Testicular Cancer? — American Cancer Society
  14. Breast Cancer Facts & Figures 2022-2024 — American Cancer Society
  15. Human T-Lymphotropic Virus Type 1 — World Health Organization
  16. Lymphomas Associated With Epstein-Barr Virus Infection in 2020: Results From a Large, Unselected Case Series in France — eClinicalMedicine
  17. Helicobacter Pylori Infection in Gastric Mucosa-Associated Lymphoid Tissue Lymphoma — World Journal of Gastroenterology
  18. Carcinogenic Mechanisms of Virus-Associated Lymphoma — Frontiers in Immunology
  19. Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions Between Pathogen, Host, and the Tumor Environment — International Journal of Molecular Sciences
  20. Borrelia Burgdorferi — StatPearls
  21. Bacterial Infection and Non-Hodgkin’s Lymphoma — Critical Reviews in Microbiology
  22. Association Between Obesity/Overweight and Leukemia: A Meta-Analysis of Prospective Cohort Studies — Blood
  23. The Risk of Lymphoma Development in Autoimmune Diseases: A Meta-Analysis — JAMA Internal Medicine
  24. Oncogenetic Landscape of Lymphomagenesis in Coeliac Disease — Gut
  25. The Risk of Developing Lymphoma Among Autoimmune Thyroid Disorder Patients: A Cross-Section Study — Disease Markers
  26. Risk of Lymphoma Subtypes After Solid Organ Transplantation in the United States — British Journal of Cancer
  27. Cancer Risk and Mortality After Solid Organ Transplantation: A Population-Based 30-Year Cohort Study in Finland — International Journal of Cancer
  28. Risk of Non-Hodgkin Lymphoma Following Treatment of Inflammatory Conditions With Tumor Necrosis Factor-Alpha Inhibitors — Blood
  29. Overview of the Janus Kinase Inhibitors for Rheumatologic and Other Inflammatory Disorders — Wolters Kluwer UpToDate
  30. 10 Cancer Prevention Recommendations — American Institute for Cancer Research
  31. Environmental Pesticide Exposure and Non-Hodgkin Lymphoma Survival: A Population-Based Study — BMC Medicine
  32. Benzene and Cancer Risk — American Cancer Society
  33. Occupational Exposures and Risks of Non-Hodgkin Lymphoma: A Meta-Analysis — Cancers
  34. Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis From the InterLymph Consortium — Environmental Health Perspectives
  35. The Obesity Controversy: Does It Impact Treatment Response in Diffuse Large B-Cell Lymphoma? — International Journal of Hematology-Oncology and Stem Cell Research
  36. Healthy Eating — American Institute for Cancer Research

A MyLymphomaTeam Member

Intersting synopsis. It is sounding like genetic transmission could be more likely. My maternal aunt was diagnosed with stage 4 Non-Hodgkins lymphoma at 79. She lived until 97 with no treatment (… read more

August 15, 2023
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