Hodgkin’s Lymphoma (HL) is a cancer originating in the lymphatic system, specifically involving B lymphocytes. The disease is defined by the presence of large, abnormal cells known as Reed-Sternberg cells. While HL development involves changes to a person’s DNA, it is generally not considered a strictly hereditary cancer, though genetics play a complex role alongside other factors.
Understanding Genetic Versus Hereditary Cancer
The terms “genetic” and “hereditary” describe different mechanisms of cancer development. Cancer is considered genetic if it is caused by alterations, or mutations, in the DNA of a cell. These genetic changes can occur at any point during a person’s life, often due to environmental exposures or random errors during cell division. Such acquired changes are known as somatic mutations and are confined only to the cancerous cells.
When cancer is hereditary, the specific DNA mutation responsible was inherited directly from a parent. These inherited changes are present in all cells of the body, including germline cells, and significantly increase the lifetime risk of developing the disease. For Hodgkin’s Lymphoma, the vast majority of cases arise from acquired, somatic genetic changes. This means the cancer itself is genetic, but not hereditary, and a person cannot typically pass HL directly to their children.
The Role of Family History and Shared Risk
Though not strictly hereditary, a family history of Hodgkin’s Lymphoma is associated with a slightly elevated risk for other family members. The overall risk for the general population to develop HL is low. Having a first-degree relative, such as a parent or sibling, who has had the disease increases the likelihood. This small increase suggests that shared genetic predispositions or common environmental exposures within a household may contribute to risk.
Studies focusing on twins provide strong evidence for a genetic component in HL susceptibility. Identical twins, who share 100% of their DNA, show a higher concordance rate for developing HL than non-identical twins. This finding points toward an inherited genetic factor, though it is not a single, high-penetrance mutation like those found in hereditary breast or colon cancer. However, the familial risk remains small, and most people with a family history will never develop the disease.
Specific Gene Changes Associated with Hodgkin’s Lymphoma
The development of Hodgkin’s Lymphoma is driven by acquired genetic changes occurring within B lymphocytes. These somatic mutations transform the normal B cell into the characteristic Reed-Sternberg cell, which proliferates uncontrollably. One of the most frequently altered cellular mechanisms involves the NF-κB signaling pathway, a protein complex that controls DNA transcription, cytokine production, and cell survival.
In many HL cases, genetic changes lead to the constant activation of the NF-κB pathway, telling the Reed-Sternberg cells to survive and divide continuously. Other genetic abnormalities, such as the loss of tumor suppressor genes or the gain of oncogenes, also contribute to the malignant transformation. These changes are found only in the tumor cells and not in the patient’s other cells.
While HL itself is not typically inherited, certain rare inherited conditions that cause primary immunodeficiencies can significantly raise the likelihood of developing it. Syndromes that impair the normal functioning of the immune system make a person more susceptible to developing various cancers, including HL. In these cases, the person inherits a faulty immune gene, but the resulting lymphoma still requires additional acquired mutations to form.
Environmental and Immune System Contributors
Since Hodgkin’s Lymphoma is not purely inherited, external factors and the state of the immune system play significant roles in its development. The Epstein-Barr Virus (EBV) is one of the most studied non-inherited factors, found in the Reed-Sternberg cells of about 25% to 40% of HL cases. EBV infection can initiate or contribute to the genetic changes needed for the cell to become cancerous.
A compromised immune system is a major non-genetic risk factor for developing Hodgkin’s Lymphoma. People with conditions that suppress the immune response, such as HIV infection, have a higher incidence of HL compared to the general population. Individuals who receive immunosuppressant drugs after an organ transplant are also at an increased risk. These external and immune-related factors underscore that HL arises from a complex interaction between a person’s genetic susceptibility and their environment.