Etiology
The etiology of Hodgkin lymphoma is unknown.
Disease is most likely linked with:
- Prior viral infection
- Genetic predisposition
Viral Environmental Factor - EBV
Prior exposure to Epstein-Barr Virus (EBV) is linked to development of Hodgkin lymphoma.
Exposure to EBV as an important etiologic component is supported by:
- Detection of EBV viral genome incorporated into human DNA in Reed-Sternberg cells.
- A gene found in Reed-Sternberg cell that codes for a latent membrane protein inducing cell transformation was identified as viral DNA from EBV. Possible development of the disease when this latent gene becomes activated.
- More than 50% of childhood cases are EBV-positive.
- 100% of HIV associated Hodgkin lymphoma are EBV-positive. The number of EBV-positive cases varies among different histological subtypes, with mixed-cellularity type being most strongly correlated.
Studies show a clustering effect in incidences of Hodgkin lymphoma based on geographic patterns in young adults but not older groups:
- Exposure to EBV at a specific age is an etiologic factor.
- Infection during adolescence is associated with subsequent development of mononucleosis.
- Infection during childhood is associated with Burkitt lymphoma.
- Patients with history of mononucleosis have a higher chance of developing Hodgkin lymphoma within five years.
However - EBV is a common infection and is associated with other malignancies; Hodgkin disease is not a common malignancy. Many people infected with EBV will not develop lymphoma.
Hodgkin lymphoma is probably the result of altered immunity in a chronically immunodeficient individual stimulated by viral factors.
Genetic Predisposition
Less than 1% of Hodgkin lymphoma is associated with a family history of this disease.
- Siblings of patients have a 3-7-fold increase in future development of Hodgkin lymphoma, especially same gender siblings.
- A higher risk (99-fold increase) in monozygotic twins but not dizygotic twins.
Individuals with inherited or pre-existing immunodeficiency disease are more susceptible to developing Hodgkin lymphoma. Increased incidence rates are seen in:
- Lymphorecticular system disorders
- Ataxia telangiectasia
Hodgkin lymphoma has a weaker genetic predisposition compared to other lymphomas.