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What Causes Lymphoma?

Posted on July 22, 2020
Medically reviewed by
Todd Gersten, M.D.
Article written by
Kelly Crumrin

Lymphoma is a type of blood cancer that involves white blood cells called lymphocytes. Lymphoma starts in the lymph nodes and vessels of the lymphatic system. When lymphocytes develop genetic mutations, the abnormal cells can grow faster and live longer than healthy cells. The two main types of lymphoma are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). There are many subtypes of NHL.

Like other cancers, lymphoma is caused by genetic mutations that allow cells to divide and grow in a disorganized way. There are two main types of mutations, inherited and acquired.

Acquired mutations:

  • Happen over the course of a person’s life
  • Are caused by normal aging and exposure to carcinogens, such as radiation, certain chemicals, smoking, and some viruses
  • Are present in the DNA of some cells

Inherited mutations:

  • Are passed down from parents to children
  • Are present in the DNA of all cells at birth
  • Occur far less commonly

Both acquired mutations and inherited factors are believed to increase the risk for developing Hodgkin lymphoma and non-Hodgkin lymphoma. It is still unclear why some people develop lymphoma and others do not.

How Cells Transform Into Cancer

Normal cells divide in a regular, ordered fashion, forming new cells that are exact copies to replace old ones. Certain genes in each cell are responsible for telling cells when to divide and when to stop dividing. Other genes identify and fix problems in DNA that is copied incorrectly, or they cause cells with bad DNA to self-destruct rather than keep multiplying. If a genetic mutation causes one or more of these genes to turn off in some cells, the cells can divide at a faster rate without regulation or order, becoming more and more mutated. Mutations may accumulate, further speeding the unchecked growth of abnormal cells. When these disordered cells begin to invade nearby tissues or break off and migrate to other locations, they have become cancerous.

Risk Factors for Lymphoma

It is important to note that while science is good at finding correlations — or apparent relationships — between factors and disease, correlation does not prove the factor causes the disease. Many risk factors for lymphoma have been identified and are being studied for their role in the development of the disease. Since genetic mutations cause lymphoma, risk factors for lymphoma include anything that can encourage mutations.

Risk factors vary by the type of lymphoma. Some risk factors are similar for Hodgkin and non-Hodgkin lymphoma. Other risk factors are more strongly associated — or only associated — with an increased risk for either HL or NHL, or for specific subtypes of NHL.

Age

Mutations in DNA are inevitable, and they accumulate with age. Researchers theorize that for cells in rapidly dividing tissues, such as blood stem cells, tens of thousands of mutations likely accumulate by age 60. However, cancer only develops in a small percentage of people.

Both Hodgkin lymphoma and non-Hodgkin lymphoma can develop at any age, from childhood through older adulthood. However, NHL becomes more common with age. NHL diagnoses are most common in those ages 65 to 74.

HL is most common among two separate age groups — teens and young adults ages 15 through 39, and older adults ages 75 or older. Most HL cases are diagnosed between ages 15 and 34.

Inherited Factors

Genes passed down through families may raise the risk for HL. Having a first-degree relative (parent or sibling) with lymphoma may make you more likely to develop HL or NHL too.

Some rare, inherited genetic disorders that affect the immune system may also raise the risk for developing lymphoma. These include Wiskott-Aldrich syndrome, Klinefelter’s syndrome, and ataxia-telangiectasia.

Sex and Ethnicity

Men have a higher risk of developing lymphoma in general. Follicular lymphoma occurs more commonly in women. Some rare forms of lymphoma only develop in men (primary testicular lymphoma) or women (primary breast lymphoma).

In the United States, white Americans are more likely than Black or Asian Americans to develop NHL.

Environmental Factors

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

Geography

Non-Hodgkin lymphoma is more common in developed countries, including the United States and nations in Europe. Researchers are not yet certain why. One theory is that infections linked to lymphoma may be more prevalent in these countries.

Infections

Infections by several viruses and bacteria have been identified as risks for developing lymphoma.

  • Epstein-Barr virus (EBV), which causes mononucleosis, is associated with an increased risk for HL. EBV is found in about 30 percent of Hodgkin lymphoma cells. EBV may also increase the risk for subtypes of non-Hodgkin lymphoma, including Burkitt’s lymphoma and natural killer (NK)/T-cell lymphoma.
  • Human immunodeficiency virus (HIV) increases the risk for developing lymphomas.
  • Human T-cell lymphotropic virus type 1 (HTLV-1) increases risk for several types of lymphoma.
  • Helicobacter pylori is a bacterium that causes stomach ulcers and is associated with the development of mantle cell lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma in the stomach.
  • 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 (HHV-8) is associated with a rare type of NHL called primary effusion lymphoma, especially in people with HIV.

Autoimmune Conditions

Certain autoimmune health conditions are associated with an increased risk for developing non-Hodgkin lymphoma. Researchers have not yet established whether this increased risk is due to inflammation caused by the condition itself or side effects of treatments for the condition. Treatments for autoimmune conditions generally work by suppressing aspects of the immune system.

Autoimmune conditions associated with a higher risk for NHL include:

  • Rheumatoid arthritis, which causes pain, swelling, and damage in the joints
  • Systemic lupus erythematosus (also known simply as lupus), which can attack the skin, kidneys, central nervous system, and other tissues
  • Sjögren’s syndrome, which can cause dry eyes, dry mouth, and other symptoms
  • Celiac disease, which causes damage to the small intestine when someone eats gluten, is associated with peripheral T-cell lymphomas.

Other Health Conditions

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

Medications

Some chemotherapy drugs used to treat cancer may increase the risk for developing NHL later on. Some medications used to treat autoimmune conditions, including Methotrexate and tumor necrosis factor inhibitors such as Infliximab, Adalimumab, Golimumab, and Certolizumab, may be associated with an increased risk of NHL. More studies are needed to better understand these associations.

Women 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 for developing NHL. Sources of ionizing radiation include radiation therapy, building materials, nuclear medicine procedures, and medical scans such as X-rays, computer tomography (CT or CAT), positron emission tomography (PET), or fluoroscopy.

Chemicals

Many chemicals have been linked to a higher incidence of lymphoma. These include herbicides and pesticides, such as organochlorine, organophosphate, phenoxy acid compounds, and the glyphosate herbicide Roundup.

Exposure to benzene — a common chemical used in plastics, rubber, dye, detergents, and gasoline — is known to cause cancer in general, and some studies have shown a connection to NHL. Cigarette smoke (including secondhand smoke) contains benzene, and accounts for about half of Americans’ exposure to the chemical.

Occupational Risk

Non-Hodgkin lymphoma is more common in agricultural communities, and farm workers tend to develop certain subtypes of NHL at a higher rate than people in other occupations. Those who work as hairdressers and in the textile industry may also have a higher risk for developing NHL. People who work in these fields or participate in related hobbies may be more likely to be exposed to carcinogenic chemicals such as those listed above.

Obesity

Obesity is defined as having a body mass index (BMI) of 30 or higher. Obesity increases the risk for developing DLBCL, a subtype of NHL. Obesity is associated 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 play a role in the development of lymphoma. Genetic testing of lymphoma cells is often part of the lymphoma diagnostic process, since it helps doctors distinguish between types of lymphoma. Knowing which mutations are present in cancer cells helps doctors recommend effective treatment options.

Can Lymphoma Be Prevented?

There is no certain way to avoid developing lymphoma. Many people who develop lymphoma have no known risk factors. Most risk factors, including age, genetic predisposition, and ethnicity, are beyond anyone’s control. If you are concerned that you may have a high risk for developing lymphoma, focus on lowering your risk by changing the environmental factors within your control.

  • If you work with radiation or carcinogenic chemicals, take every precaution to limit your exposure. Use protective equipment and follow safety procedures consistently.
  • General guidelines for cancer prevention recommend eating a healthy diet with plenty of fresh fruits, vegetables, and whole grains, and limiting your intake of red meat and processed meats. A balanced, nutritious diet can also encourage a healthy weight.
  • Stop smoking and avoid exposure to secondhand tobacco smoke.

If your doctor has told you that you have risk factors for developing lymphoma, make sure to attend all follow-up appointments to receive monitoring tests. You may not notice symptoms on your own. Diagnosing cancer early may mean there are more options for treatment.

Lymphoma Condition Guide

References
  1. About Lymphoma — Lymphoma Research Foundation
  2. Germline and Somatic Mutations: What Is the Difference? — Oncology Nursing Society
  3. Hodgkin Lymphoma Risk Factors — American Cancer Society
  4. Non-Hodgkin Lymphoma Risk Factors — American Cancer Society
  5. Follicular Lymphoma: A Review of Mechanisms, Risk Factors, and Unmet Needs — AJMC
  6. How do genes control the growth and division of cells? — Genetics Home Reference
  7. Aging and the rise of somatic cancer-associated mutations in normal tissues — PLOS Genetics
  8. Hodgkin Lymphoma — Leukemia & Lymphoma Society
  9. Radiation Studies: Ionizing Radiation — Centers for Disease Control and Prevention (CDC)
  10. Lymphoma — Centers for Disease Control and Prevention (CDC)
  11. Association Between Obesity/Overweight and Leukemia: A Meta-Analysis of Prospective Cohort Studies — Blood — American Society of Hematology (ASH)
  12. The Risk of Lymphoma Development in Autoimmune Diseases A Meta-analysis — JAMA Internal Medicine
  13. Non-Hodgkin Lymphoma Booklet — Leukemia & Lymphoma Society
  14. Risk of Non-Hodgkin Lymphoma Following Treatment of Inflammatory Conditions with Tumor Necrosis Factor-Alpha Inhibitors — Blood — American Society of Hematology (ASH)
  15. Does Gender Matter in Non-Hodgkin Lymphoma? Differences in Epidemiology, Clinical Behavior, and Therapy — Rambam Maimonides Medical Journal
  16. 10 Cancer Prevention Recommendations — American Institute for Cancer Research
  17. Benzene and Cancer Risk — American Cancer Society
  18. Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium — Environmental Health Perspectives
  19. Healthy Eating — American Institute for Cancer Research

A MyLymphomaTeam Member said:

I also had Epstein Barr that put me in the hospital. Also had 6 weeks of radiation treating breast cancer. Now I have follicular lymphoma.

posted 8 days ago

hug

Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Kelly Crumrin is a senior editor at MyHealthTeams and leads the creation of content that educates and empowers people with chronic illnesses. Learn more about her here.

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