Genetic overlap between autoimmune diseases and non‐Hodgkin lymphoma subtypes

Abstract

Epidemiologic studies show an increased risk of non‐Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen‐stimulation in one disease leads to another. Here we assess shared genetic risk in genome‐wide‐association‐studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B‐cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta‐analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta‐analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS‐based analysis four NHL subtypes and three ADs revealed few weakly‐associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis

“…Similarly, Ikeura et al [65] reported three cases (4.8%) of PC development during an average of 95 months of follow up in 63 AIP patients, whereas Ishida et al [66] reported the development of malignant lymphoma in the parotid gland seven months after the diagnosis of AIP. Even after successful discrimination of AIP from malignancies, clinicians must remain aware of the possible development of cancers [65,67,68] or lymphomas [68][69][70][71] during the follow up of the patients with AIP or IgG4-related diseases, as epidemiological [64,65,[67][68][69][70] or genetic [71] risks have been reported.…”

Tracking the Genetic Susceptibility Background of B-Cell Non-Hodgkin’s Lymphomas from Genome-Wide Association Studies

“…Furthermore, there have been vast population studies to associate the presence of different etiologies, such as smoking, height, weight, autoimmune conditions, alcohol consumption, viral infections, and genetics, with the risk of developing any subtype of NHL [ 3 , 9 , 10 ]. Nevertheless, despite these efforts, there are only few established risk factors including autoimmune conditions (e.g., Sjögren disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis), immunodeficiency syndromes, organ transplants, breast implants and specific infections (e.g., Helicobacter pylori for mucosa-associated lymphoid tissue lymphoma of the stomach, immunodeficiency virus, and mononucleosis) [ 11 , 12 , 13 ].…”

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review

“…There is a mutual relationship between connective tissue diseases and HMs. On the one hand, patients with a long-term history of connective tissue diseases including lupus erythematosus (LE), Sjogren's syndrome and systemic sclerosis demonstrate an increased risk of HMs, with special regard to B-cell lymphoma [203][204][205][206]. In patients with systemic LE, the closest association is with diffuse large B-cell lymphoma [207].…”

“…On the other hand, marginal zone lymphomas and those associated with mucosal-associated lymphoid-tissue lymphomas are the predominant subtypes observed in patients with Sjogren’s syndrome, where the incidence is up to 44-fold higher than the general population [ 208 , 209 ]. The pathogenesis of B-cell neoplasms in patients with connective tissue diseases is likely multifactorial, including some shared genetic/environmental factors, chronic inflammation, long-term immunosuppression and persistent high levels of cytokines such as IL-6, BAFF, APRIL and Blc2, which are involved in both autoimmune disease and lymphomagenesis, and, for systemic LE, Epstein–Barr virus infection [ 204 , 207 ].…”