B-cell lymphoma is a cancer originating in B cells, a type of white blood cell crucial for the immune system’s antibody production. When abnormal B lymphocytes multiply uncontrollably, they form tumors within the lymphatic system. This system, present throughout the body, allows B-cell lymphoma to develop in various locations, leading to diverse symptoms.
Understanding B-Cell Lymphoma and Heredity
B-cell lymphoma is not typically inherited directly, meaning it does not usually pass from parents to children in a predictable pattern. For most individuals, B-cell lymphoma arises from genetic mutations that occur during a person’s lifetime. These acquired changes are known as somatic mutations. Somatic mutations affect only the cells where they originate and are not passed to offspring.
In contrast, germline mutations are inherited from a parent and are present in nearly every cell, including reproductive cells, allowing them to be passed down. While genetic studies of diffuse large B-cell lymphoma (DLBCL) have identified numerous somatic mutations, some germline alterations have also been uncovered. However, these germline mutations are not the primary drivers for most B-cell lymphomas, which are largely considered “sporadic” cases resulting from these acquired, somatic changes.
Abnormal somatic hypermutation, a process where B cells undergo many gene changes to produce antibodies, can lead to genetic alterations that make it difficult for the body to remove faulty cells and repair damaged DNA, contributing to the development of lymphoma.
Genetic Susceptibility
While B-cell lymphoma is not directly inherited, genetics can influence an individual’s susceptibility. Inherited genetic variations can slightly increase the likelihood of developing the disease, but they do not directly cause it. These common genetic differences have small effects on risk.
Rare inherited genetic syndromes significantly elevate lymphoma risk. Examples include Wiskott-Aldrich syndrome and ataxia-telangiectasia, both associated with primary immunodeficiencies and DNA repair disorders. Li-Fraumeni syndrome is another condition linked to an increased risk of various cancers, including lymphomas. These syndromes involve single-gene defects that lead to genetic instability and increased mutation rates.
Familial clustering can also occur, where multiple family members develop lymphoma without a clear single inherited gene explaining the pattern. This clustering might be due to subtle genetic predispositions or shared environmental factors within a family. For instance, having a first-degree relative with non-Hodgkin lymphoma can nearly double the risk of developing diffuse large B-cell lymphoma, and the risk increases if the relative specifically had DLBCL.
Non-Genetic Factors Contributing to Risk
Since most B-cell lymphoma cases are not hereditary, various non-genetic factors play a role in their development.
Age is a factor; the risk increases with advancing age, with most cases occurring in individuals 60 or older. This is partly due to the accumulation of genetic changes over a lifetime.
A weakened immune system also elevates risk. Conditions like HIV/AIDS, organ transplants requiring immunosuppressive drugs, and certain autoimmune diseases, including Sjögren’s syndrome, rheumatoid arthritis, and systemic lupus erythematosus, can increase lymphoma risk, possibly due to chronic immune system activation or immunosuppressive medications.
Specific infections are recognized risk factors for certain B-cell lymphoma subtypes. The Epstein-Barr virus (EBV), for example, is linked to Burkitt lymphoma and extranodal natural killer/T-cell lymphoma. Human Herpesvirus 8 (HHV-8) is associated with primary effusion lymphoma, while Helicobacter pylori bacterial infection is a known risk factor for gastric MALT lymphoma. These infections can either directly alter lymphocyte DNA or lead to chronic immune stimulation, increasing the chance of cancerous changes.
Environmental exposures also contribute to risk. Exposure to certain chemicals, such as benzene and some pesticides and herbicides, has been suggested to increase the risk of non-Hodgkin lymphoma, though research continues to clarify these links. High doses of radiation, such as from atomic bomb exposure or radiation therapy for other cancers, also elevate the risk of developing lymphoma later in life. Maintaining a healthy lifestyle, including a balanced diet, regular physical activity, and avoiding tobacco, can support overall health and potentially reduce the risk of various cancers, including lymphomas.