Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype.
BACKGROUND
Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL). Because different NHL subtypes develop at different stages of lymphocyte differentiation, associations of autoimmune and inflammatory disorders with specific NHL subtypes could lead to a better understanding of lymphomagenic mechanisms.


METHODS
In a population-based case-control study in Denmark and Sweden, 3055 NHL patients and 3187 matched control subjects were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. Logistic regression with adjustment for study matching factors was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for NHL overall and for NHL subtypes.


RESULTS
Risks of all NHL were increased in association with rheumatoid arthritis (OR = 1.5, 95% CI = 1.1 to 1.9), primary Sjögren syndrome (OR = 6.1, 95% CI = 1.4 to 27), systemic lupus erythematosus (OR = 4.6, 95% CI = 1.0 to 22), and celiac disease (OR = 2.1, 95% CI = 1.0 to 4.8). All of these conditions were also associated with diffuse large B-cell lymphoma, and some were associated with marginal zone, lymphoplasmacytic, or T-cell lymphoma. Ever use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and selected immunosuppressants was associated with risk of NHL in rheumatoid arthritis patients but not in subjects without rheumatoid arthritis. Also, multivariable adjustment for treatment had little impact on risk estimates. Psoriasis, sarcoidosis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype.


CONCLUSIONS
Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.
Smedby
Karin Ekström
KE
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. karin.ekstrom@meb.ki.se
Hjalgrim
Henrik
H
Askling
Johan
J
Chang
Ellen T
ET
Gregersen
Henrik
H
Porwit-MacDonald
Anna
A
Sundström
Christer
C
Akerman
Måns
M
Melbye
Mads
M
Glimelius
Bengt
B
Adami
Hans-Olov
HO
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications*; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D003718:Denmark; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008214:Lymphocytes / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000150:complications*; D013548:Sweden; D013997:Time Factors
D001324:Autoantigens