Any substance or condition that increases cancer risk is referred to as a risk factor. There isn’t a known, single cause of non-Hodgkin lymphoma (NHL). Most cancers are the result of many risk factors. However, some people with NHL do not have any identifiable risk factors.
*Risk factors are generally listed in order from most significant to least significant. In most cases, it is impossible to rank the relative significance of individual risk factors with absolute certainty.
The risk of developing NHL increases with age. It is more common in people who are in their 60s and above. Overall, NHL is more common in men than women, though some specific types of NHL are more common in women.
The following factors are known to increase the risk of developing NHL.
Weakened immune system
People who have a weakened immune system are at an increased risk of developing NHL. It does not matter if the immune system was damaged at birth (congenital) or later in life (acquired). The immune system can be weakened for a number of reasons.
Immunosuppressant drugs
Immunosuppressant drugs suppress the immune system. They are used to prevent a person’s immune system from attacking a new organ after a transplant. But, immunosuppressant drugs also decrease the body’s natural ability to defend itself. People who take immunosuppressant drugs after a solid organ (kidney, heart, liver) transplant are at an increased risk for a type of NHL called post-transplant lymphoproliferative disorder (PTLD).
HIV/AIDS
People with HIV (human immunodeficiency virus) or AIDS (acquired immunodeficiency syndrome) have a greater risk of developing some types of B-cell lymphoma such as Burkitt’s lymphoma and diffuse large B-cell lymphoma. HIV/AIDS weakens the body’s immune system. People with HIV/AIDS have a significantly increased risk of developing NHL and some other types of cancer. There has been a significant decline in AIDS-related lymphomas because of highly active antiretroviral therapy (HAART) – a combination of anti-HIV drugs used to treat HIV infection.
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Immunodeficiency disorders
An immunodeficiency disorder affects the immune system’s natural ability to defend the body against infection. People with immunodeficiency disorders often have frequent infections, which can be severe or unusual, and they have an increased risk of developing cancer. An immunodeficiency disorder may be present at birth (congenital), in which case it is usually hereditary. Or, it may develop later in life (acquired) as a result of another disorder such as diabetes or treatments that suppress the immune system. Inherited immunodeficiency disorders are very rare, whereas acquired ones are somewhat more common.
How NHL develops is related to the specific disorder and which part of the immune system is affected. The following immunodeficiency disorders increase the risk of developing NHL.
Ataxia-telangiectasia (AT)
AT is a rare inherited disorder that causes problems with muscle coordination (ataxia) because of abnormalities in a part of the brain called the cerebellum. The person with AT will have neurological problems that gradually get worse. AT also causes dilated capillaries (telangiectasia) or spider veins to appear, especially on the eyes and ears.
Wiskott-Aldrich syndrome (WAS)
WAS is a rare inherited disorder that usually only affects boys. WAS causes low platelet counts (thrombocytopenia) and related bleeding problems, a skin condition called eczema and recurrent respiratory infections.
Common variable immunodeficiency (CVID)
CVID is an acquired disorder that usually develops after birth, even into adulthood. CVID can cause the development of autoimmune diseases (such as rheumatoid arthritis), problems with the gastrointestinal tract and recurrent lung infections.
Severe combined immunodeficiency (SCID)
SCID is a very rare inherited condition that causes thrush (yeast) infections, diarrhea and pneumonia in infants and young children. It is the most serious immunodeficiency disorder.
X-linked lymphoproliferative disorder
X-linked lymphoproliferative disorder is a very rare inherited condition in which children develop very serious infectious mononucleosis because of infection with the Epstein-Barr virus. They can later develop liver failure, bone marrow failure and other conditions.
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Autoimmune disorders
An autoimmune disorder causes the body’s immune system to attack its own tissue. Some autoimmune disorders have been linked to an increased risk of NHL, but the number of cases of NHL associated with autoimmune disorders is small. People with autoimmune disorders may be treated with immunosuppressant drugs, which may contribute to an increased risk of NHL.
The following are autoimmune disorders associated with NHL.
Sjogren’s syndrome
Sjogren’s syndrome is a chronic disorder that damages the salivary glands and tear glands, which results in a very dry mouth and eyes. It can affect other organs and parts of the body such as joints, muscles, nerves, lungs, kidneys, liver, pancreas, stomach, brain and thyroid gland.
Sjogren’s syndrome is associated with marginal zone lymphomas that occur in the salivary glands or other sites such as the stomach and lung. It is also associated with diffuse large B-cell lymphoma.
Rheumatoid arthritis
Rheumatoid arthritis (RA) causes inflammation, pain and stiffness of the joints. However, the inflammation may also affect other organs, such as the eyes, lungs or heart. RA is associated with diffuse large B-cell lymphoma and lymphoplasmacytic lymphoma.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE or lupus) can affect various parts of the body and cause inflammation of the skin, joints, blood vessels, nervous system and internal organs such as the heart, lungs and kidneys. SLE is associated with diffuse large B-cell lymphoma.
Celiac disease
Celiac disease damages the small intestine and interferes with the absorption of nutrients from food. People with celiac disease have an immune response to gluten – a protein found in wheat, rye and barley. Celiac disease is associated with an increased risk of a rare type of T-cell lymphoma called enteropathy-associated T-cell lymphoma (EATL).
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Certain infections
Some infections can increase the risk of NHL. These viral or bacterial infections may either cause damage to the lymphocytes or chronic stimulation of the immune system and can increase the risk of developing NHL.
Human T-cell leukemia/lymphoma virus, type 1 (HTLV-1)
HTLV-1 increases the risk of developing adult T-cell lymphoma and leukemia. This virus is most common in southern Japan and the Caribbean.
Epstein-Barr virus (EBV)
EBV causes infectious mononucleosis (mono or the “kissing disease”). EBV is linked to Burkitt’s lymphoma and to lymphomas in people whose immune system is suppressed because of HIV/AIDS or immunosuppressant drugs. EBV is also linked to some other types of cancer. This virus and Burkitt’s lymphoma most commonly occur in Africa.
Helicobacter pylori
H. pylori is a bacterium that causes stomach ulcers and inflammation of the stomach lining (gastritis). It is associated with gastric lymphomas, particularly a type of lymphoma that occurs in the stomach called mucosa-associated lymphoid tissue (MALT) lymphoma. H. pylori also increases the risk of stomach cancer.
Human herpes virus 8 (HHV8)
HHV8 is associated with primary effusion lymphoma, body cavity lymphomas and AIDS-related lymphomas. This virus is also believed to cause another type of cancer called Kaposi sarcoma.
Hepatitis C virus (HCV)
HCV is one of a group of viruses that can cause inflammation of the liver (hepatitis). People with HCV infection are at an increased risk of developing B-cell lymphoma and other types of NHL.
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Previous treatment for Hodgkin lymphoma
People who have been treated with chemotherapy and radiation therapy for Hodgkin lymphoma are at an increased risk of developing NHL. The risk is greatest in the first 5 years after treatment, but there is an increased risk for the rest of the person’s life. However, the benefit of having these treatments for cancer usually far outweighs the risk of developing a second cancer.
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Possible risk factors
The following factors have some association with NHL, but there is not enough evidence to say they are known risk factors. Further study is needed to clarify the role of these factors for NHL.
- exposure to pesticides – Pesticides include a large number of different chemicals, some of which may be related to lymphoma risk. Some studies have suggested that exposure to certain pesticides, such as Agent Orange, may be associated with an increased risk of developing NHL. The evidence has not been consistent, so further research is needed to help clarify the possible link between pesticides and cancer, and to identify which ones may increase the risk of NHL.
- family history of NHL – NHL is not generally considered to be familial (occurring in families more often than would be expected by chance). However, some studies have shown an increased risk of NHL in people with first-degree relatives (parent, brother or sister, child) who have been diagnosed with lymphoma. Further studies are needed to better assess the risk of developing NHL when a first-degree relative has had NHL.
- exposure to trichloroethylene – Trichloroethylene (TCE) is a solvent used mostly to remove grease from metal. Some studies have suggested that exposure to TCE may increase the risk of developing NHL.
- diet – Some studies have suggested that diets high in meat, dairy products and saturated fat may increase the risk of developing NHL. Other studies have found that diets low in vegetables increase the risk of NHL. However, the link between NHL and diet is very complex, and researchers are trying to find out how diet may increase the risk.
- obesity – Some studies have suggested that being obese may increase the risk of NHL, in particular large B-cell lymphoma.
- occupational exposure to hair dyes – An increased risk of cancer was noted in relation to using hair dye, particularly permanent, dark colours, before 1980, when hair dye formulas changed. This risk was seen in hair dressers and barbers, who were exposed to the dye at work. More research is needed to find out if occupational exposure to hair dye increases the risk of NHL. The chemical composition of hair dyes is different now than before 1980, and some of the harmful ingredients have been removed.
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Unknown risk factors
The following are factors for which there is not enough evidence or the evidence is inconclusive. In other words, it can’t be determined for sure whether these risk factors are or are not associated with NHL.
- personal exposure to hair dye (dark, permanent colours)
- occupational exposures
- farming
- rubber industry
- wood and forestry
- printing
- physical activity
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See a list of questions to ask your doctor about risks.