Lymphoma is a type of cancer originating in the lymphatic system, a critical part of the immune system responsible for fighting infections and maintaining fluid balance. Lymphoma primarily affects lymphocytes, a subtype of white blood cells. There are two main categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). While both types originate in the lymphatic system and can share similar symptoms, they differ significantly in their behaviour, treatment approaches, and underlying causes.1,2
Non-Hodgkin lymphoma (NHL) is the more common of the two and represents a diverse group of blood cancers affecting lymphocytes, particularly B and T cells. It is the most common type of blood cancer worldwide. NHL is more commonly diagnosed in men, people over 65, and individuals with weakened immune systems or a family history of blood cancers. But what causes NHL? Scientists have uncovered several potential risk factors, but the exact cause often remains unknown. This article will explore the known and suspected causes of non-Hodgkin lymphoma in greater depth.3,4,5
The lymphatic system is a network of vessels, tissues, and organs that protects the body from infections and diseases. It includes lymph nodes, the spleen, bone marrow, and lymphatic vessels that transport lymph fluid.1
Lymphocytes travel through this system, identifying and attacking viruses, bacteria, and other threats. There are two main types of lymphocytes: B cells and T cells. NHL can develop from either type, and depending on the origin, different subtypes of NHL are identified.2,6
In the NHL, lymphocytes undergo genetic mutations that cause them to multiply uncontrollably and live longer than they should. These abnormal cells build up in lymph nodes and other tissues, interfering with the body’s ability to fight infections.7
One of the main reasons NHL develops is because of changes, or mutations, in the genes of specific white blood cells called lymphocytes. These gene changes affect how the cells grow, divide, and die. Usually, old or damaged cells die off, but when these genes are changed, cells do not die like they should and start to grow out of control.
Some changes can happen by chance, while things like infections, harmful chemicals, or radiation may trigger others. For instance, a change in a gene called BCL2 can stop B cells from dying, so they build up over time. Another example is a swap of genetic material between chromosomes 14 and 18, which is often seen in a type of NHL called follicular lymphoma.
These mutations usually happen during a person’s life rather than being passed down from parents. However, in rare cases, inherited conditions like Li-Fraumeni syndrome or ataxia-telangiectasia can raise the risk of NHL.6,7,8
People with compromised immune systems are at higher risk of developing NHL. A weakened immune system can result from:
The main problem is immune dysregulation. Whether the immune system is suppressed or chronically activated, it creates conditions where lymphocytes can become cancerous.2,3,5,7
Certain infections have been strongly linked to specific types of non-Hodgkin lymphoma. These infections may either directly cause lymphocyte changes or lead to long-term immune system activation.
These infections do not cause NHL in everyone, but they may be a triggering factor in individuals with genetic susceptibility or immune dysfunction.1,7,9
Environmental exposures to certain chemicals and radiation have been implicated in the development of NHL. People who work in agriculture, manufacturing, or the chemical industry may be more frequently exposed to carcinogens such as:5,8,9
While most cases of NHL are not inherited, having a family history of lymphoma or other blood cancers can slightly increase your risk. This may be due to shared environmental exposures, common genetic traits, or both.
Inherited conditions impairing DNA repair or immune regulation, like Bloom syndrome or Wiskott-Aldrich syndrome, also raise NHL risk, although they are rare.
It’s important to note that having a family history does not ensure that an individual will develop NHL, but it may play a role in a complex risk profile.3,5,9
NHL can occur at any age, but it is far more common in older adults, especially those over 65. As people age, their immune systems weaken, and genetic mutations accumulate, increasing the likelihood of cancerous changes in cells.
Additionally, men are slightly more likely to develop NHL than women. The reasons for this are not fully understood, but hormonal, genetic, and occupational exposure differences may play a role.2,3,10
Despite all the known risk factors, most people with NHL have no apparent cause for their disease. This makes NHL a complex cancer that likely results from a combination of genetic, environmental, immune, and possibly random factors.
The disease may sometimes start from a single mutated cell that happens by chance. It may take years of exposure or immune disruption in others before lymphoma appears. Due to this complexity, the NHL is still being studied to better understand its origins and progression.1
While it is not always possible to prevent NHL, especially when the cause is unknown, there are steps you can take to reduce your overall risk:1,11
Lymphoma is a type of cancer that starts in the lymphatic system, which is essential for the immune system. It mainly affects lymphocytes, a kind of white blood cell. There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL is the more common type and includes various blood cancers affecting B and T cells. It is often diagnosed in men, older individuals, and those with weakened immune systems or a family history of blood cancers, although the exact causes of NHL are still not fully understood. The lymphatic system includes vessels, tissues, and organs like lymph nodes and the spleen, which help fight infections. NHL occurs when lymphocytes undergo genetic mutations, leading to uncontrolled growth and longevity of these cells. Some mutations can happen randomly, while infections, harmful chemicals, and radiation can also trigger them. Certain rare inherited conditions can increase the risk. People with weakened immune systems, such as those with HIV/AIDS or autoimmune diseases, are more likely to develop NHL. Specific infections like Epstein-Barr virus and exposure to certain chemicals like pesticides may increase NHL risk. While family history can play a role, most NHL cases appear without clear causes. Although NHL is more common in older adults and slightly more in men, prevention strategies include protecting the immune system, limiting chemical exposure, and adopting healthy habits.
