Cancer is one of the leading causes worldwide. It is estimated that nearly 10 million deaths occurred in 2020, or nearly one in six deaths, according to the World Health Organisation (WHO). Lymphoma is a group of cancers that affect a type of white blood cell called lymphocytes. It is also called the cancer of the lymphatic system. It is characterised by an aberrant (unusual) development of lymphocytes, where they do not function properly and can proliferate uncontrollably.

Understanding lymphoma and its causes

Our immune system is the main defence system in our body, and a crucial part of it is the lymphatic system, a network of vessels, tissues, and organs that includes lymph nodes, the spleen, the thymus, and bone marrow.¹ Its job is to filter waste, transport immune cells, and fight off invaders like bacteria and viruses. But what happens when these very defenders, the immune cells, turn against the body? This is the unsettling reality of lymphoma.

Lymphoma is, quite simply, a cancer of the lymphatic system. It's a type of cancer that originates in lymphocytes, a type of white blood cell that plays a crucial role in our immune defence.² Instead of maturing and working properly, these lymphocytes grow abnormally and multiply out of control, and disrupt the body's natural processes. It’s a disease that touches the very core of our protective mechanisms, making it both complex for those affected and those treating people with the condition.

The word "cancer" often brings with it a surge of fear and uncertainty, and for good reason. Yet, understanding what lymphoma is and, perhaps more importantly, what might contribute to its development, can be a powerful first step in navigating this journey.

The two main types are Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL).^2,3,4 While both originate in lymphocytes, they behave differently and are treated with different approaches.

Hodgkin Lymphoma is often characterised by the presence of a specific type of abnormal cell called the Reed-Sternberg cell. It typically spreads in an orderly fashion from one lymph node group to the next.⁵

Non-Hodgkin Lymphoma, on the other hand, is a much more diverse group, encompassing a wide array of subtypes.⁶ It can originate in either B-lymphocytes (B-cells) or T-lymphocytes (T-cells), though B-cell lymphomas are far more common. Unlike Hodgkin lymphoma, NHL can arise in lymph nodes throughout the body and even in organs outside the lymphatic system.⁷

Understanding this fundamental split is crucial, as the specific type of lymphoma profoundly influences its prognosis and the chosen course of treatment.

Exploring the causes of lymphoma

When facing a diagnosis like lymphoma, one of the most natural and persistent questions that arises is, "Why me?" The truth is, for the vast majority of lymphoma cases, there isn't a single, clear-cut answer. It's not like a bacterial infection with a known culprit. Instead, lymphoma, like many cancers, is thought to result from a complex interplay of genetic predispositions, environmental exposures, and lifestyle factors.^2,8 It's rarely one thing, but rather a combination of elements that, over time, can nudge cells down a pathway toward uncontrolled growth.

Risk factors

While we can't pinpoint a definitive cause for every person, extensive research has identified several risk factors that can increase a person's likelihood of developing lymphoma. Risk factors may include:

Immune system 

Perhaps one of the most significant and well-established risk factors for certain types of lymphoma is a compromised immune system, when your body's natural defences are not functioning optimally.

• Epstein–Barr virus (EBV): About half of cases of Hodgkin lymphoma are due to Epstein–Barr virus (EBV)
• HIV/AIDS: Individuals with HIV, the virus that causes AIDS, have a significantly higher risk of developing certain aggressive types of non-Hodgkin lymphoma. The virus directly attacks and weakens the immune system, leaving it vulnerable
• Organ transplant recipients: People who have undergone organ transplants often need to take immunosuppressive drugs for the rest of their lives to prevent their body from rejecting the new organ. While lifesaving, these medications weaken the immune system, which can increase the risk of lymphoma, particularly a type called post-transplant lymphoproliferative disorder (PTLD)
• Certain genetic conditions: Children born with certain inherited conditions, like ataxia-telangiectasia (AT) and Wiskott-Aldrich syndrome, have compromised immune systems. This not only makes them more susceptible to severe infections but also raises their risk of developing NHL
• Helicobacter pylori and Hepatitis C: Associated with the development of other types of lymphoma

Environmental exposure

• Exposure to chemicals like benzene, and certain herbicides and insecticides, have correlative relationships with NHL risk. However, research is still ongoing to clarify these relationships.
• Some chemotherapy drugs used to treat other cancers might increase the risk of developing NHL years later. For instance, individuals treated for HL have a higher subsequent risk of NHL. It's not definitively known if this increased risk is due to the Hodgkin lymphoma itself or a side effect of its treatment.
• The link between certain drugs used for rheumatoid arthritis (RA), such as methotrexate and TNF inhibitors, and an increased NHL risk is less clear. While some studies suggest a connection, others haven't found one. This is complicated because people with RA, an autoimmune disease, already have a higher inherent risk of NHL.

Age

Age is a significant risk factor for lymphoma generally, with most cases occurring in people aged 60 or older. However, it's worth noting that certain types of lymphoma buck this trend and are more prevalent in younger people. For instance, Hodgkin lymphoma (HL) can be diagnosed at any age, but it shows two common peaks: one in early adulthood (particularly in people's 20s) and another in late adulthood (after age 55).⁹

Biological sex

When it comes to sex, men generally have a higher risk of developing Non-Hodgkin lymphoma (NHL) than women,⁹ though there are specific NHL subtypes more common in women. The reasons behind these differences aren't yet understood. HL also occurs slightly more often in males than in females.

Race, ethnicity, and geography

Race, ethnicity, and geography also play a role. In the United States, White individuals are more likely to develop NHL compared to African American and Asian American individuals. Globally, NHL is more prevalent in developed countries, with some of the highest rates found in the United States and Europe. This geographic variation can sometimes be linked to certain infections that are more common in specific regions, which in turn are risk factors for certain lymphoma types.

Family History

A family history of lymphoma can increase your risk. If you have a first-degree relative (a parent, child, or sibling) with NHL, your own risk of developing NHL is heightened. Similarly, siblings of young people with HL face a higher risk, and this risk is particularly elevated for an identical twin of someone with HL. However, a family link is uncommon, and most individuals with HL do not have a family history of the disease. The exact reasons why family history influences risk aren't entirely clear, but possibilities include shared childhood exposures to certain infections (like Epstein-Barr virus) or shared inherited genetic changes that increase susceptibility, or a combination of these factors.

Summary

While many risk factors are beyond our control, our age, our genes, past infections, understanding them can empower us. For instance, if you're undergoing immunosuppressive therapy, your doctors will be monitoring you closely. If you live in an area with certain endemic infections, awareness can be key.

For the general population, maintaining a healthy lifestyle, a balanced diet, regular physical activity, avoiding smoking, and limiting alcohol consumption are always good strategies for overall health.

Ultimately, the most important message for anyone concerned about lymphoma is to be aware of their body. Persistent swollen lymph nodes (especially if painless and growing), unexplained fever, night sweats, unexplained weight loss, and fatigue are symptoms that warrant a visit to a doctor. Early detection and diagnosis are often key to successful treatment outcomes.