About Lymphoma

Possible causes of lymphoma?

Doctors aren’t sure what causes lymphoma but it begins when a disease-fighting white blood cell called a lymphocyte develops a genetic mutation. The mutation tells the cell to multiply rapidly, causing many diseased lymphocytes that continue multiplying.

The mutation also allows the cells to go on living when other normal cells would die. This causes too many diseased and ineffective lymphocytes in lymph nodes and causes the lymph nodes, spleen and liver to swell.

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How does lymphoma develop?

Lymphoma can develop when lymphocytes, which are a type of white blood cell, gain a DNA mutation. The role of the lymphocytes is to fight infection, as part of the body’s immune system. The lymphoma cells then divide and grow out of control or do not die as they should. The build-up of these abnormal cells causes lymphoma and lumps mainly in the lymph nodes. Lymphoma is the name given to a group of diseases that are caused by abnormal (cancerous) lymphocytes.

Researchers are finding out more about the genetic changes in lymphoma. These findings are helping in developing new and better treatments for lymphoma. In most cases it is not known what actually causes these changes. Most genetic changes probably happen by chance. Several genetic changes are usually needed before lymphoma develops.

Dr Mary Ann Anderson, haematology
Peter MacCallum Cancer Centre & Royal Melbourne Hospital

What are risk factors?

There have been many studies that have looked at how lymphoma develops. Through these studies, scientists have found some possible ‘risk factors’ that have been associated with some subtypes of lymphoma. Risk factors are something that may increase a person’s chances of developing a disease or health condition.

Overall, the cause of how someone has developed lymphoma is unknown. The risk of developing lymphoma is low and if you were to have a risk factor it means that you are more likely to develop lymphoma than someone who doesn’t have a risk factor. Most people who have these risk factors do not develop lymphoma. For most people who develop lymphoma, the cause is unknown.

The main risk factor for lymphoma are problems with your immune system. This is unlike other types of cancer, where lifestyle factors are more of a risk factor to develop cancer.

Who does it affect?

There are currently over 80 different subtypes of lymphoma. Some of these subtypes are very rare. Lymphoma can affect people at any age. There are certain subtypes that can affect people more commonly at different ages.

The incidence of lymphoma increases as we get older. Most cases of lymphoma occur over the age of 60 years. There are some types of lymphoma that are more common in children and younger people. For example, Hodgkin lymphoma is the most common lymphoma in young adults aged between 15 and 30 years.

The incidence of non-Hodgkin lymphoma (NHL) is higher in men than it is in women. But there are certain types of NHL that are more common in women than in men.

For more info see
Types of Lymphoma

Family History

Lymphoma is not inherited from your parents. Your risk of developing lymphoma is slightly higher if you have a family member or close relative (parent, brother, sister or child) who has lymphoma. This increased risk is not usually linked to a gene abnormality. Research suggests that the increased risk may be caused by inheriting several genetic differences between different people (polymorphisms) that can all contribute to a small increase in risk. These genetic differences are often in genes of the immune system. However, some lifestyle factors may also contribute to an increased risk to the development of a lymphoma.

Some people who have had cancer can also develop a second, different cancer later in their life and this could be lymphoma.

Immune system disorders

The immune system protects us from infections. It is also responsible to kill abnormal cells that are not needed any more, are damaged, or are not working properly (such as cancer cells). Conditions that cause problems with your immune system can cause your lymphocytes to not work properly, grow out of control, resulting in lymphoma. Health conditions that may cause problems with your immune system may include:

  • Immunosuppressive medications
  • Immunodeficiency disorders
  • Autoimmune disorders

 

 

Immunosuppressive medications

People who have had an organ transplant or an allogeneic (donor) stem cell transplant need to take immunosuppressive medications. These medications suppress (decrease) the immune system response so as to prevent your body from rejecting the new donor organ or cells by reacting against them.

Some people need to take immunosuppressive medications for other reasons, such as autoimmune disorders. Being on these medications can increase your risk of developing lymphoma. The increased risk can depend upon factors such as what type of transplant you had and how much immunosuppressive medication you need. Lymphomas that develop after a transplant are called post-transplant lymphoproliferative disorders (PTLDs).

Immunodeficiency disorders

Primary Immunodeficiency disorder

People who have primary immunodeficiency disorders are born with or have a genetic cause to develop these (changes in your genes). There are many different types of these disorders. There is data that shows a higher risk of developing non-Hodgkin lymphoma (NHL) in patients with congenital (born with) immune deficiencies than in people who are not born with these disorders.

Children with congenital X-linked immunodeficiency and severe combined system immunodeficiency are at a higher risk of developing NHL. NHL is also increased in young people with ataxia telangiectasia or Wiskott-Aldrich syndrome. These are rare disorders and so account for very few cases of lymphoma.

Secondary immunodeficiency disorders are immune system problems that are caused by another condition or treatment than one that you are born with. This can include HIV or chemotherapy.

HIV and lymphoma

Human immunodeficiency virus (HIV) infection is characterised by a specific deficiency of CD4 positive T-cells and the chronic stimulation of B-cells. People with HIV are less able to fight infections that are linked to certain types of cancer, and some lymphomas in people with HIV are caused by viruses. HIV infection is associated with an increased risk of developing non-Hodgkin lymphoma (NHL).

HIV infection is a risk factor for developing certain types of NHL, including primary central nervous system (CNS) lymphoma (of the brain or spinal cord), Burkitt lymphoma, and diffuse large B-cell lymphoma.

Autoimmune disorders

Autoimmune disorders cause a person’s immune system to be overactive and attack parts of their own body. In some people this can be an increased risk of developing lymphoma. The risk of developing non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma increases 2 to 3 times more in rheumatoid arthritis patients. NHL incidence increases in people with certain autoimmune disorders that can include:

Infection causes

Epstein-Barr virus (EBV)

The Epstein-Barr virus (EBV), is a type of herpes virus with B-cell-transforming activity. This is a common virus that can be found worldwide. There is strong evidence that there is an increased risk associated with non-Hodgkin lymphoma (NHL) and EBV infection. There is an increased risk when a person’s immune system is compromised, such as after a transplant or with HIV infection and EBV infection. It is a high risk factor, after getting EBV infection and for a type of Burkitt lymphoma in some parts of Africa.

The Epstein-Barr virus is the cause of glandular fever. Most people in the world are infected by EBV at some stage. However, in most people, the infection does not usually cause any symptoms. EBV is found in the lymphoma cells of:

  • Burkitt lymphoma seen in children in Africa and sometimes in the sporadic type of Burkitt lymphoma.
  • Hodgkin lymphoma: around one third of Hodgkin lymphomas are linked to EBV
  • HIV-associated lymphoma
  • Post-transplant lymphoproliferative disorder (PTLD)
  • T-cell lymphomas: certain subtypes have been known to be associated with EBV
Helicobacter pylori (H pylori)

Helibacter pylori (H pylori) infection is associated with a 6-fold increase in risk of gastric B-cell NHL, known as mucosa-associated lymphoid tissue (MALT) lymphoma.

Human T-lymphotropic virus types I/II

Infection with the human retrovirus HTLV-I/II is rare in Australia. In regions where HTLV-I is endemic, such as southern Japan and the Caribbean, infection is associated with increased risk of adult T-cell leukemia/lymphoma, a form of non-Hodgkin lymphoma (NHL). HTLV-1 spreads through sex and contaminated blood and can be passed to children through breast milk from an infected mother.

Hepatitis C virus (HCV)

Hepatitis C virus (HCV) infection is the main cause of mixed cryoglobulinemia. This is a benign lymphoproliferation (uncontrolled growth of cells) that can change into B-cell non-Hodgkin lymphoma (NHL). There is mixed evidence for an association between HCV infection and NHL.

Campylobacter jejuni

The campylobacter jejuni virus is a common cause of food poisoning and is linked to MALT lymphoma in the bowel.

Borrelia burgdorferi

The borrelia burgdorferi is a bacteria infection which causes Lyme disease and is linked to MALT lymphoma in the skin.

Human herpesvirus-8 (HHV8)/Kaposi’s sarcoma herpesvirus (KSHV)

HHV8 is a human herpesvirus that is widespread in homosexual men in Australia. In addition to Kaposi’s sarcoma, it is associated with a rare form of B-cell non-Hodgkin lymphoma (NHL) called primary effusion lymphoma. This occurs in adults with immunosuppression related to HIV infection or organ transplantation.

Exposure to infection

There is limited evidence of an association between non-Hodgkin lymphoma (NHL) risk and factors indicating potential for infection and immunological stimulation, such as socioeconomic status and childhood crowding. Risk of Hodgkin lymphoma in young adulthood is associated with indicators of higher childhood social class. This includes things such as single-family housing, small family size, early birth order, and high maternal education. These associations generate the hypothesis that HL in young adults is caused by delayed exposure to common childhood infections.

Occupational and environmental exposure

Pesticides, herbicides, and agricultural exposures

There is a known association with an increased risk of some non-Hodgkin lymphoma (NHL) and chemical exposure. This risk factor has been linked to both the use and production of pesticides and herbicides.

There are some occupations that have seen an increased risk of developing both non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Farmers have been linked to being at a higher risk due to being exposed to pesticides, herbicides, fungicides, infectious microorganisms, solvents, paints, fuels, oils, and dusts. All these agents have been associated with increased risk of NHL and HL.

Other occupations that involve work with animals, such as meat (abattoir) workers, meat inspectors, and veterinarians have been associated with increased risk of both NHL and HL. Exposure to animal-borne viruses has been linked.

Other chemicals

The relationship between occupational exposure to solvents and NHL or HL is not clear. However, occupational exposure to hair dyes is inconsistently associated with an increased risk of both NHL and HL. The risk associated with occupational exposure to chemical compounds in hair dyes is shown by the potential for increased exposure to infectious agents through personal contact with clients.

Other occupational exposures

Although mixed, the balance of evidence favours a moderate positive association between occupation in a wood-related industry and Hodgkin lymphoma (HL). The evidence about such an association for non-Hodgkin lymphoma (NHL) is weak and inconsistent.

Studies have identified increased risk of NHL in industries with exposure to welding and asbestos, particles, as well as metal workers, rubber workers those in electrical occupations, as well as occupations of higher social class.

Other causes of lymphoma

Breast implant-associated anaplastic large cell lymphoma

A new subtype of lymphoma has recently been classified that can be associated with breast implants. This is called breast implant-associated anaplastic large cell lymphoma (ALCL), that is T-cell non-Hodgkin lymphoma. The implant can cause pockets of fluid and infection or inflammation that over time can develop into ALCL. If this is found people will have the implant removed and any lumps or fluid removed by surgery. This can often be the only treatment some people need. If more widespread, you are likely to have chemotherapy.

Discussed further in
Anaplastic Large Cell Lymphoma

Previous cancers

Some people can develop a second cancer, that has developed often years after the first cancer. A second cancer is different to a relapse of the first cancer, which is when the cancer comes back.

Second cancers can also be late effects of the treatment that you received for the first cancer, that can occur many years later. This can happen because treatments like chemotherapy and radiotherapy damage cells, including lymphocytes. Treatment for cancer can therefore increase your risk of developing a second cancer in the future.

If you have had treatment for cancer, your medical team should give you information on what to look out for and how to reduce your risk of developing late effects.

Non-cancerous conditions

Monoclonal B-cell lymphocytosis

Monoclonal B-cell lymphocytosis (MBL) is a non-cancerous condition. This condition causes an increased number of abnormal B-cells called lymphocytes in the blood. The abnormal B-lymphocytes have the same characteristics as chronic lymphocytic leukaemia (CLL). MBL can be seen as a precursor (pre-cancerous) condition of CLL, where it can change into CLL over time.

The incidence of monoclonal B-cell lymphocytosis (MBL) increases with age. MBL is very rare in people under 40 years of age and only affects around 1% of the population. Around 10% of people affected are over the age of 40 years. Approximately 75% of people affected are over the age of 90 years.

MBL is managed by yearly appointments with a specialist to monitor the condition. If the MBL does progress to become CLL, it is likely that the management will be ongoing monitoring. The majority of people who progress to CLL, will live the rest of their natural life span. This is a result of treatments available today and the advances in future treatments.

For more info see
Monoclonal B-cell Lymphocytosis (MBL)

Lifestyle

Some lifestyle factors have been linked with an increased risk of developing lymphoma but evidence is limited. It is likely that any increased risks are small. However, many of the following factors are important in the development of various types of cancer.

It is important to keep a healthy lifestyle by maintaining a healthy weight, exercising regularly, eating a healthy diet and not smoking can reduce your risk of many health problems.

Smoking

The relationship between cigarette smoking and risk of non-Hodgkin lymphoma (NHL) is unclear. Findings from some recent studies suggest increased risk for follicular lymphoma and high-grade lymphomas. Results from studies support a positive association between cigarette smoking and Hodgkin lymphoma (HL).

Alcohol

Some studies have found a protective effect of alcohol consumption, in particular wine, on risk of NHL. There have been no studies of alcohol consumption and risk of HL.

Physical activity

Physical activity and obesity are likely to influence immune function. Physical activity appears unrelated to NHL risk. Study data about excess weight are equivocal. A single cohort study examining all cancers found a significant association between obesity and HL in men. There have been no studies of physical activity and risk of HL.

Nutrition

Diets high in fat or meat products appear to double the risk of NHL, but, the data is inconsistent. A single study examined fish consumption and found no association with NHL.

Results from studies have shown no clear association between fruit and vegetable intake and risk of NHL. There is a tendency towards a protective effect.

The balance of evidence suggests there is no protective or harmful effect on NHL from vitamin supplement use.

Studies are consistent in showing no association between risk of NHL and tea and coffee consumption. The association with milk consumption is unclear. Nitrate, a contaminant in drinking water, can break down into carcinogenic compounds.

However, studies conducted to date have found no association with nitrate levels in drinking water and NHL risk.

There is no pattern of risk for diet and HL.

In most cases, the cause of lymphoma is not known. There is little or no evidence to suggest that anything you have done – or not done – has caused you to develop lymphoma. Talk to your doctor if you are worried about the possible cause of your lymphoma or about the risk for someone close to you.

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