Non-Hodgkin Lymphoma Risk Factors

A risk factor is anything that increases your chance of getting a disease like cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t.

But having a risk factor, or even many risk factors, does not mean that you will get the disease. And many people who get the disease may have few or no known risk factors.

Researchers have found several factors that can affect a person’s chance of getting non-Hodgkin lymphoma (NHL). There are many types of lymphoma, and some of these factors have been linked only to certain types.

Age 

Getting older is a strong risk factor for lymphoma overall, with most cases occurring in people in their 60s or older. But some types of lymphoma are more common in younger people.

Sex

Overall, the risk of NHL is higher in men than in women, but there are certain types of NHL that are more common in women. The reasons for this are not known.

Race, ethnicity, and geography

In the United States, White people are more likely than African American people and Asian American people to develop NHL.

Worldwide, NHL is more common in developed countries, with the United States and Europe having some of the highest rates. Some types of lymphoma are linked to certain infections (described further on) that are more common in some parts of the world.

Family history

Having a first-degree relative (parent, child, sibling) with NHL increases your risk of developing NHL.

Exposure to certain chemicals and drugs

Some studies have suggested that exposure to chemicals such as benzene and certain herbicides and insecticides (weed- and insect-killing substances) may be linked to an increased risk of NHL. Research to clarify these possible links is still in progress.

Some chemotherapy drugs used to treat other cancers may increase the risk of developing NHL many years later. For example, people who have been treated for Hodgkin lymphoma have an increased risk of later developing NHL. But it’s not totally clear if this is related to the disease itself or if it is an effect of the treatment.

Some studies have suggested that certain drugs used to treat rheumatoid arthritis (RA), such as methotrexate and the tumor necrosis factor (TNF) inhibitors, might increase the risk of NHL. But other studies have not found an increased risk. Determining if these drugs increase risk is complicated by the fact that people with RA, which is an autoimmune disease, already have a higher risk of NHL (see below).

Radiation exposure

Studies of survivors of atomic bombs and nuclear reactor accidents have shown they have an increased risk of developing several types of cancer, including NHL, leukemia, and thyroid cancer.

People treated with radiation therapy for some other cancers, such as Hodgkin lymphoma, have a slightly increased risk of developing NHL later in life. This risk is greater for people treated with both radiation therapy and chemotherapy.

Having a weakened immune system

People with weakened immune systems have an increased risk for NHL. For example:

• People who receive organ transplants are treated with medicines that suppress their immune system to prevent it from attacking the new organ. These people have a higher risk of developing NHL.
• The human immunodeficiency virus (HIV) can weaken the immune system, and people infected with HIV are at increased risk of NHL.
• In some genetic (inherited) syndromes, such as ataxia-telangiectasia (AT) and Wiskott-Aldrich syndrome, children are born with a deficient immune system. Along with an increased risk of serious infections, these children also have a higher risk of developing NHL.

Autoimmune diseases

Some autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), Sjogren (Sjögren) disease, celiac disease (gluten-sensitive enteropathy), and others have been linked with an increased risk of NHL.  

In autoimmune diseases, the immune system mistakenly sees the body’s own tissues as foreign and attacks them, as it would a germ. Lymphocytes (the cells from which lymphomas start) are part of the body’s immune system. The overactive immune system in autoimmune diseases may make lymphocytes grow and divide more often than normal. This might increase the risk of them developing into lymphoma cells.

Certain infections

Some types of infections may increase the risk of NHL in different ways.

Infections that directly transform lymphocytes

Some viruses can directly affect the DNA (genes) in lymphocytes, helping to transform them into cancer cells:

• Infection with human T-cell lymphotropic virus (HTLV-1) increases a person’s risk of certain types of T-cell lymphoma. This virus is most common in some parts of Japan and in the Caribbean region, but it’s found throughout the world. In the United States, it causes less than 1% of lymphomas. HTLV-1 spreads through sex and contaminated blood and can be passed to children through breast milk from an infected mother.
• Infection with the Epstein-Barr virus (EBV) is an important risk factor for Burkitt lymphoma in some parts of Africa. In developed countries such as the United States, EBV is more often linked with lymphomas in people also infected with HIV, the virus that causes AIDS. EBV has also been linked with some less common types of lymphoma.
• Human herpes virus 8 (HHV-8) can also infect lymphocytes, leading to a rare type of lymphoma called primary effusion lymphoma. This lymphoma is most often seen in people who are infected with HIV. HHV-8 infection is also linked to another cancer, Kaposi sarcoma. For this reason, another name for this virus is Kaposi sarcoma-associated herpes virus (KSHV).

Infections that weaken the immune system

Infection with human immunodeficiency virus (HIV), the virus that causes AIDS, can weaken the immune system. HIV infection is a risk factor for developing certain types of NHL, such as primary CNS lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma.

Infections that cause chronic immune stimulation

Some long-term infections may increase a person’s risk of lymphoma by forcing their immune system to be constantly active. As more lymphocytes are made to fight the infection, there is a greater chance for mutations in key genes to occur, which might eventually lead to lymphoma. Some of the lymphomas linked with these infections actually get better when the infection is treated.

• Helicobacter pylori, a type of bacteria known to cause stomach ulcers, has also been linked to mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach.
• Chlamydophila psittaci (formerly known as Chlamydia psittaci) is a type of bacteria that can cause a lung infection called psittacosis. It has been linked to MALT lymphoma in the tissues around the eye (called ocular adnexal marginal zone lymphoma).
• Infection with the bacterium Campylobacter jejuni has been linked to a type of MALT lymphoma called immunoproliferative small intestinal disease. This type of lymphoma, which is also sometimes called Mediterranean abdominal lymphoma, typically occurs in young adults in eastern Mediterranean countries.
• Long-term infection with the hepatitis C virus (HCV) seems to be a risk factor for certain types of lymphoma, such as splenic marginal zone lymphoma.

Body weight

Some studies have suggested that having excess body weight might increase your risk of NHL. More research is needed to confirm these findings. In any event, staying at a healthy weight, keeping physically active, and following a healthy eating pattern that includes plenty of fruits, vegetables, and whole grains, and that limits or avoids red and processed meats, sugary drinks, and highly processed foods has many known health benefits outside of the possible effect on lymphoma risk.

Breast implants

Although it is rare, some women with breast implants might develop lymphoma in the scar tissue (capsule) that forms around the implant. Most of these are a rare type of T-cell lymphoma known as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), but other types of NHL have been reported as well.