Lymphoma is a general term for cancers originating in the lymphatic system, a network of tissues and organs that helps the body fight infection. Lymphoma develops from lymphocytes, a type of white blood cell. When the DNA within these cells changes, they begin to grow and multiply uncontrollably, leading to the formation of tumors. Certain circumstances and characteristics, known as risk factors, increase the likelihood of this cellular transformation. Understanding these factors is important for identifying populations who may be at an elevated risk.
Age and Other Non-Modifiable Factors
Age is the primary factor for Non-Hodgkin lymphoma (NHL), with the majority of cases occurring in people over 60 years old. The risk for NHL increases steadily throughout a person’s lifetime, likely due to the natural accumulation of genetic changes in cells over decades. Hodgkin lymphoma (HL) exhibits a bimodal age distribution, meaning it is most common in two distinct age groups: young adults (typically 15 to 34) and older adults (over 55 or 60).
Men are generally at a slightly higher risk for most types of lymphoma than women. Geographic and ethnic differences exist, with rates of NHL higher in developed countries and in White people compared to African American and Asian American populations in the United States. Having a first-degree relative who has had lymphoma moderately increases an individual’s risk, suggesting a genetic predisposition. However, most lymphomas are not inherited, and the majority of people with a family history never develop the disease.
Immune System Compromise and Autoimmunity
Conditions that suppress the immune system represent a major category of acquired lymphoma risk. When the immune system is significantly weakened, it loses the ability to recognize and destroy abnormal cells, allowing cancerous lymphocytes to proliferate unchecked. Human Immunodeficiency Virus (HIV) infection is a major example, as it severely depletes helper T-cells and is strongly associated with aggressive lymphomas like Burkitt lymphoma and diffuse large B-cell lymphoma.
Organ transplant recipients who must take immunosuppressive medications long-term are another high-risk group. This deliberate suppression limits the immune system’s surveillance function, leading to a higher incidence of lymphomas, often those linked to viral infections. Certain inherited conditions, known as primary immunodeficiency syndromes, can also lead to a weakened immune response from birth, predisposing individuals to increased risk.
Chronic activation of the immune system, such as that seen in autoimmune diseases, is also a factor in lymphoma development. Autoimmune disorders like Sjögren’s syndrome, Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA) cause lymphocytes to be constantly stimulated. This persistent B-cell activity increases the rate of cell division, which raises the opportunity for genetic mutations to occur and lead to malignancy. Sjögren’s syndrome carries a particularly elevated risk for certain B-cell non-Hodgkin lymphomas.
Specific Infectious Agents
Specific viruses and bacteria are recognized for their ability to directly contribute to the malignant transformation of lymphocytes. The Epstein-Barr Virus (EBV), a common virus that causes infectious mononucleosis, is strongly implicated in several lymphoma subtypes. EBV is linked to nearly all cases of endemic Burkitt lymphoma, a subset of Hodgkin lymphoma, and Post-Transplant Lymphoproliferative Disorder (PTLD) in immunosuppressed individuals.
Human T-cell Lymphotropic Virus Type 1 (HTLV-1) specifically targets T lymphocytes and is the established cause of Adult T-cell Leukemia/Lymphoma. This disease is endemic in parts of Japan, Africa, and the Caribbean. The bacterium Helicobacter pylori (H. pylori) is a risk factor for gastric Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. H. pylori causes chronic inflammation in the stomach lining, and treating the infection with antibiotics can often cause the lymphoma to regress.
The Hepatitis C Virus (HCV), known for causing chronic liver infection, is also associated with an increased risk of certain B-cell non-Hodgkin lymphomas. This includes splenic marginal zone lymphoma and diffuse large B-cell lymphoma. The mechanism is thought to involve chronic immune stimulation rather than direct cellular transformation.
Environmental and Occupational Exposures
Exposure to certain external chemicals and physical agents in the environment or workplace has been associated with an increased risk of developing Non-Hodgkin lymphoma. Among the most studied are specific pesticides and herbicides, particularly those used in agriculture. Studies have suggested a link between occupational exposure to these agents, including phenoxy herbicides and chemicals like glyphosate, and elevated lymphoma risk.
Certain organic solvents and industrial chemicals, such as benzene and trichloroethylene, have also been identified as potential risk factors. These exposures are most relevant to workers in specific manufacturing, petrochemical, or agricultural settings who experience higher and more prolonged contact with these substances. Benzene, for example, is found in gasoline, rubber cement, and some industrial processes, and its exposure has been consistently linked to an increased risk of blood cancers.
A person’s medical history can also involve exposures that elevate risk, particularly prior treatment for a different cancer. Chemotherapy and radiation therapy, while lifesaving treatments, can slightly increase the chance of developing a secondary lymphoma years later. However, the benefit of receiving these treatments for the original cancer far outweighs the small risk of developing a secondary malignancy. Having any combination of these factors does not guarantee a diagnosis, but it indicates a slightly higher probability compared to the general population.