B-cell lymphoma is a group of cancers originating in B-lymphocytes, a type of white blood cell crucial for the immune system. These cells are found within the lymphatic system, including organs like lymph nodes, spleen, and bone marrow. When B-lymphocytes undergo changes causing uncontrolled growth, they form tumors. Understanding if B-cell lymphoma is “genetic” involves two distinct categories of genetic alterations: those inherited from parents and those acquired during a person’s lifetime.
Decoding Genetic Changes in Cancer
Genetic changes, or mutations, are alterations in a cell’s DNA. They are categorized by their origin. Inherited (germline) mutations are present in every cell from birth, passed down from a parent through their egg or sperm. These mutations persist throughout life and can be passed to children.
Acquired (somatic) mutations develop during a person’s lifetime and are not inherited. These changes occur in specific cells, such as B-lymphocytes, and are not present in every body cell. Acquired mutations cannot be passed to offspring. In cancer, “genetic” refers to both inherited predispositions and these acquired changes within tumor cells.
Inherited Predispositions
A small percentage of B-cell lymphoma cases are linked to inherited genetic factors. While most lymphomas are not directly passed from parent to child, having a close relative with lymphoma or another blood cancer can slightly increase an individual’s risk. This familial link suggests that shared genetic variations might contribute to susceptibility.
Specific inherited gene mutations, such as pathogenic variants in ATM, TP53, BRCA1, and BRCA2, have been associated with an elevated lymphoma risk. Individuals with certain rare genetic syndromes, like Ataxia-telangiectasia or Wiskott-Aldrich syndrome, also have a higher likelihood of developing B-cell lymphomas due to their weakened immune systems. However, these inherited factors account for a minority of all B-cell lymphoma diagnoses.
Acquired Genetic Mutations and Lymphoma Development
The majority of B-cell lymphomas arise from genetic changes occurring within B-cells during a person’s lifetime. These acquired somatic mutations disrupt the normal functions of critical genes, leading to uncontrolled B-cell growth. Such disruptions often involve proto-oncogenes (which promote cell growth) or tumor suppressor genes (which regulate cell division and repair DNA damage).
A common acquired alteration involves chromosomal translocations. These occur when chromosome pieces break off and reattach to different chromosomes, often placing an oncogene next to a highly active gene like an immunoglobulin gene. For example, translocations involving MYC, BCL2, or BCL6 genes are frequently observed in various B-cell lymphoma subtypes, including Burkitt lymphoma and diffuse large B-cell lymphoma. These rearrangements lead to the overexpression of these oncogenes, driving abnormal B-cell proliferation.
Beyond translocations, other acquired genetic alterations, such as deletions, amplifications, and point mutations, also contribute to lymphoma development. These mutations can affect signaling pathways crucial for B-cell function, including the B-cell receptor (BCR) signaling, PI3K pathway, and NF-kB pathway. Mutations in genes related to chromatin remodeling and transcriptional control are also found. The accumulation of these mutations over time can lead to the transformation of healthy B-cells into cancerous ones.
Non-Genetic Risk Factors
While genetic alterations are central to B-cell lymphoma development, many other factors influence an individual’s risk. Age is a significant factor, with most non-Hodgkin lymphomas, including B-cell lymphomas, becoming more common in older individuals. This trend is partly attributed to the accumulation of acquired genetic changes over a lifetime.
Certain infections also increase B-cell lymphoma risk. For instance, Epstein-Barr virus (EBV) is linked to Burkitt lymphoma, and Helicobacter pylori bacterial infection is associated with MALT lymphoma. Autoimmune conditions, where the immune system mistakenly attacks its own tissues, also elevate lymphoma risk. These include Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, and celiac disease.
Conditions that weaken the immune system, such as HIV or immunosuppressant medications after organ transplantation, can increase lymphoma susceptibility. Some environmental exposures, like benzene and polychlorinated biphenyls, have been investigated as potential risk factors, though their direct causal link remains an area of ongoing research.