Is There a Link Between Familial Autoimmunity and Lymphoma?

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Research is needed to identify the potentially overlapping molecular pathways involved in autoimmunity and B-cell neoplasms.
Research is needed to identify the potentially overlapping molecular pathways involved in autoimmunity and B-cell neoplasms.

Personal history of some types of autoimmune disorder (AID) is associated with some B-cell neoplasms, specifically Hodgkin lymphoma (HL), non-HL (NHL), and multiple myeloma (MM). Yet few studies have explored the association between familial history of AID and the risk of lymphoma or myeloma. A population-based study published in the Blood Cancer Journal suggests that such an association is complex, as some familiar AIDs may increase or decrease the risk for B-cell neoplasms.1

Autoimmunity

Autoimmunity occurs when the immune system's self-tolerance to a specific self-antigen is lost, resulting in the immune system's recognition and subsequent destruction of autologous tissue. This process results in an AID, which can span from a single tissue to multiple organs.2

The estimated worldwide prevalence of AIDs is between 3% and 5%, with substantially more women affected than men, though there are exceptions. Familial AID can occur and may manifest as the same disorder or different disorders within a family. Some patients will develop multiple AIDs.

Genetic predisposition is a clear factor for developing autoimmunity, though environmental factors are also critical. Environmental factors that may promote autoimmunity include chemical pollutants, chronic hormonal stimulation, and less exposure to microbial and parasitic antigens.

Autoimmunity and Lymphoma Risk

The presence of some personal AIDs is associated with an increased risk of developing B-cell neoplasms including HL, NHL, and MM.3

The heterogeneity within both AIDs and lymphomas and MM render the study of this association challenging, though several clear associations are emerging. Evidence from multiple studies suggests that the relative risk for developing lymphoma is highest among patients with primary Sjögren syndrome (pSS; up to 16-fold), followed by systemic lupus erythematosus (SLE; up to 7-fold), and then rheumatoid arthritis (RA; about 2-fold). Some evidence suggests that higher cumulative AID disease activity is associated with a greater risk for lymphoma, particularly in RA and pSS.

Data for an association with other AIDs including Crohn disease, psoriasis, and sarcoidosis are conflicting.

RELATED: Hodgkin Lymphoma: Intensifying Treatment With Rituximab After PET

The exact mechanism linking AID to lymphoma is not yet well understood, though activation of the B-cell receptor signaling pathways is thought to be involved. The chronic inflammation associated with autoimmunity requires chronic B-cell activation and clonal expansion of B cells, and thus the potential acquisition of genetic mutations. Localized and peripheral B cells are implicated in lymphomagenesis in the setting of chronic inflammation.

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