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Causes and risk factors for lymphoma
In this article we look at the possible causes and risk factors for why some people develop lymphoma.
What causes lymphoma?
In most cases there is no known cause. If you have lymphoma, it’s not because of anything you did or didn’t do. You can’t catch lymphoma and you can’t give it to anybody else.
Lymphoma develops when white blood cells called lymphocytes grow out of control. This happens if the DNA inside a lymphocyte changes in a way that stops it responding to signals. This means that the lymphocyte divides in an abnormal way or does not die when it should.
DNA changes (mutations) happen all the time. Most of the time they’re harmless but sometimes they can affect critical genes. One DNA change on its own is not usually enough to cause lymphoma. It takes a number of different changes before a cancer starts to grow.
In most cases, it’s not known what causes these changes. Most of them probably happen by chance, although in some cases a cause can be identified. There are also some factors that might make you more likely to develop the DNA changes that lead to lymphoma. These are called ‘risk factors’. Most risk factors for cancer work by increasing the rate of natural mutation events.
Most people who develop lymphoma have none of these risk factors and the cause is unknown.
Causes of lymphoma
In medical terms, a cause is something that leads to an illness. Without the cause, the illness doesn’t happen. Removing the cause can often cure the illness.
For a few types of lymphoma, scientists have identified a cause:
- Most cases of gastric MALT lymphoma are caused by a common bacterial infection called Helicobacter pylori. Helicobacter pylori can cause stomach ulcers and indigestion, and is easily treated. Most people with Helicobacter pylori infection do not get lymphoma. Treating the infection usually causes regression of the lymphoma and may even cure the lymphoma.
- Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is caused by having textured breast implants. Although it develops in the breast, BIA-ALCL is a type of lymphoma, not a type of breast cancer. Scientists think it might be caused by an inflammatory reaction to the implant. It typically develops 8 to 10 years after having the implant but it can develop sooner or later. Most people with breast implants do not develop BIA-ALCL – but everyone who develops BIA-ALCL has had breast implants. In many cases, removing the breast implants cures the lymphoma and no further treatment is needed.
Risk factors for lymphoma
A risk factor is not the same as a cause. A risk factor is something that might increase your chance of getting an illness. A risk factor means there is a link (or ‘association’) between the factor and the illness. Removing the risk factor might not affect the illness.
There are several risk factors linked to lymphoma. Having one or more risk factors for lymphoma does not mean you will develop it. It means you are a bit more likely to develop lymphoma than someone with no risk factors. Even if you have risk factors, your chance of developing lymphoma is usually still very small.
Risk factors for lymphoma include the following:
Age
Lymphoma can develop at any age, but most types of non-Hodgkin lymphoma are more common in older people. This is because mutations tend to build up throughout your life. Some of these changes can lead to lymphoma. Hodgkin lymphoma, however, is most common in people aged between 15 and 34, or over 60.
Family history
Your risk of developing lymphoma is slightly higher if you have a close relative (parent, brother or sister, or child) who has had lymphoma or another type of blood cancer. This might be due to lots of small inherited genetic changes that all increase your risk of lymphoma slightly.
Gender
Lymphoma is slightly more common in males than females.
Infections
There are some infections that can increase your chance of developing lymphoma.
There are a few reasons for this:
- Some viruses infect lymphocytes, the type of cell that grows out of control if you have lymphoma. Occasionally, these viruses can cause changes to the DNA of the cells so they become cancerous.
- Some infections make your immune system too active. This means your body is constantly making new lymphocytes, which increases the chance of changes developing in their DNA. Occasionally, these DNA changes can lead to lymphoma.
- Some infections weaken your immune system. This makes it harder for your body to fight off other infections, including infections that might be linked to lymphoma.
Many of the infections linked to lymphoma are very common. Most people who have these infections do not get lymphoma. Scientists don’t know why some people who have certain infections get lymphoma while most don’t.
A number of different viral infections have been linked to lymphoma. They include:
- Epstein–Barr virus (EBV), a very common virus that infects B lymphocytes and can cause glandular fever. About 9 in 10 adults have been infected with EBV but many people don’t know they’ve had it. After you’ve been infected with EBV, it stays in your body, but it is normally kept under control by your immune system. People who have been infected with EBV have a higher chance of developing several types of lymphoma. However, the vast majority of people who have had EBV never get lymphoma.
- Hepatitis C virus (HCV), a virus that infects the liver. It has been linked to nodal marginal zone lymphoma, splenic marginal zone lymphoma, lymphoplasmacytic lymphoma, and diffuse large B-cell lymphoma (DLBCL). However, the vast majority of people who have had HCV never get lymphoma.
- Human herpesvirus 8 (HHV-8), a virus that infects lymphocytes and is linked with a very rare form of lymphoma called primary effusion lymphoma (PEL).
- Human T-lymphotropic virus type 1 (HTLV-1), a virus that infects T lymphocytes. It is a rare infection in the UK. It is strongly linked to a very rare lymphoma called adult T-cell leukaemia/lymphoma.
Some bacterial infections have also been linked to lymphoma. They include:
Helicobacter pylori, which can cause gastric MALT lymphoma.
Chlamydia psittaci, which causes a rare lung infection called psittacosis. It’s spread by birds, including pet birds like parrots. It is linked to MALT lymphoma in the tear ducts and around the eyes.
Campylobacter jejuni, a common cause of food poisoning. It has been linked to MALT lymphoma in the small bowel.
Borrelia burgdorferi, the bacteria that causes Lyme disease, an infection spread by ticks, might be linked to MALT lymphoma in the skin.
Moraxella catarrhalis, a bacteria that can cause chest infections, is linked to an uncommon form of Hodgkin lymphoma.
A lowered immune system
If you have a lowered immune system, you are less able to fight infections. This includes infections that increase your chance of developing lymphoma. Two particular conditions that lower your immune system and have a higher risk of lymphoma are:
- human immunodeficiency virus (HIV)
- post-transplant lymphoproliferative disorders (PTLDs).
Autoimmune conditions
Autoimmune conditions are illnesses that develop when your immune system mistakenly attacks your own body. Most people with autoimmune conditions do not develop lymphoma. However, some autoimmune conditions are linked to a higher chance of developing certain types of lymphoma. This might be because autoimmune conditions can cause long-term activation of the immune system or that people with autoimmune conditions are likely to be on medicines that dampen the immune system. Several autoimmune disorders might increase your chance of developing lymphoma:
- Sjögren’s syndrome
- Hashimoto’s thyroiditis
- refractory coeliac disease
- rheumatoid arthritis and systemic lupus erythematosus.
MGUS
Monoclonal gammopathy of unknown significance (known as ‘MGUS’) is a condition where the body makes an abnormal antibody, called a monoclonal protein or paraprotein. MGUS does not cause any symptoms and is usually diagnosed when tests are performed for other reasons. A very small number of people with a type of MGUS called IgM MGUS can go on to develop a low-grade (slow-growing) type of lymphoma.
Previous cancer treatment
Some treatments, such as chemotherapy drugs, radiotherapy, or CAR-T cell therapy, used to treat other types of cancer, including other blood cancers, might increase your chance of developing lymphoma in the future. However, most people who’ve been treated for another cancer do not develop lymphoma.
Weight
Having a body mass index of over 30 increases your risk of developing many types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia (CLL). Keeping a healthy lifestyle by maintaining a healthy weight, exercising regularly and eating a healthy diet can reduce your risk of many health problems.
Chemicals
Exposure to high levels of industrial chemicals, solvents, weedkillers and insecticides are possible risk factors for developing lymphoma. Hair dyes and hair straightening treatments might be a risk factor, although more research is required. There has also been some research suggesting that the dyes used in tattoos might be a risk factor, both when having a tattoo and when having it removed. However, the evidence on all these chemicals is limited and scientists aren’t sure if there is a link with lymphoma or not.
With thanks to Dr Eve Gallop-Evans, Consultant Clinical Oncologist, Velindre Cancer Centre, Cardiff, for reviewing this information.
Listen to our latest podcast: Changing times – 40 years on
As we celebrate our 40th anniversary, our editor Anne Hook spoke with Professor David Linch, Emeritus Professor at University College London. They discuss how things have changed clinically, with Professor Linch commenting on how lymphoma was seen as a mysterious disease with little information available for patients to learn more about it. They talk about how Lymphoma Action started in order to provide trustworthy information and support, which is very much at the heart of the Charity today.
Professor Linch talks about how treatment has changed over time, believing that a key change was in the late 60s/early 70s when combination chemotherapy was introduced. Another major step was the improvement of supportive care, meaning that more people were able to tolerate cancer treatment.
