Familial AID and Lymphoma Risk

Few studies have focused on familial AIDs or autoimmunity and risk of lymphoma. According to the authors of the study published in Blood Cancer Journal, “Even though a personal history of an AID is a known risk factor for B-cell neoplasms, the data on associations of a family history of AID with cancer risk…deserved limited attention.”

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Data of patients with AID from the Swedish Hospital Discharge Register and Outpatient Register and family relationships from the Multigeneration Register were evaluated for first-degree relatives of offspring-parents and offspring and their siblings. The goal of the study was to evaluate the risk of NHL, HL, and MM in families where a first-degree relative had a diagnosis of an AID, as well as a reverse association.

The data included over 64,000 neoplasms and 531,000 AIDs. The most common B-cell neoplasm identified in the cohort was NHL, followed by MM and then HL.

Both increased and decreased risk for lymphoma varied in the cohort depending on the type of AID within the family history. The risk for NHL was increased in families with a history of angiitis hypersensitive, discoid lupus erythematosus, Guillain-Barre syndrome, psoriasis, and Sjögren syndrome. Risk for HL was increased with familial pemphigus, and none of the AIDs evaluated increased the risk for MM.

Familial ankylosing spondylitis, acute glomerular nephritis, and Graves disease were, however, associated with a decreased risk for HL.

The reverse analysis of association between HL, NHL, or MM and familial AID provided similar data, and therefore did not contradict the results. An exception was the family history of NHL and decreased risk for psoriasis.

“The present results revealed large differences to those published on the risk of B-cell neoplasms subsequent to a personal AID, also from the present Swedish population,” wrote the authors. This discrepancy is not necessarily surprising, according to the authors, because “a personal history is a combination of a family history and a life-long history of somatic events, including immune challenges.”

The authors also noted that these data suggest that gene-environment interactions may increase or decrease the risk of developing B-cell neoplasms. “For clinical practice, the take-home message could be that a family history of some AIDs may influence the risk of B-cell neoplasms but the magnitude of risk tends to be far lower than that found for a personal history,” indicated the authors.

Unanswered Questions

Some of the data in this study conflict with findings from previous studies. Previous reports suggested an association between familial sarcoidosis and ulcerative colitis with HL, and SLE with MM.4,5 The authors noted, however, that the current study was much larger and the follow-up period spanned different years.

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This contradiction warrants the need for further studies in other populations to evaluate the risk of B-cell neoplasms in families with a history of AIDs. Additional research is also needed to more clearly identify the potentially overlapping molecular pathways involved in autoimmunity and B-cell neoplasms.


  1. Hemminki K, Forsti A, Sundquist K, Sundquist J, Li X. Familial associations of lymphoma and myeloma with autoimmune diseases. Blood Cancer J. 2017;7:e515. doi: 10.1038/bcj.2016.123
  2. Bolon B. Cellular and molecular mechanisms of autoimmune disease. Toxicol Pathol. 2012;40:216-29. doi: 10.1177/0192623311428481
  3. Baecklund E, Smedby KE, Sutton LA, Askling J, Rosenquist R. Lymphoma development in patients with autoimmune and inflammatory disorders—what are the driving forces? Semin Cancer Biol. 2014;24:61-70. doi: 10.1016/j.semcancer.2013.12.001
  4. Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst. 2006;98:1321-30. doi: 10.1093/jnci/djj361
  5. Landgren O, Linet MS, McMaster ML, Gridley G, Hemminki K, Goldin LR. Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study. Int J Cancer. 2006;118:3095-98. doi: 10.1002/ijc.21745