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American Journal of Epidemiology Advance Access originally published online on October 26, 2005
American Journal of Epidemiology 2005 162(12):1153-1161; doi:10.1093/aje/kwi341
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Immune-Related Conditions and Immune-Modulating Medications as Risk Factors for Non-Hodgkin's Lymphoma: A Case-Control Study

Eric A. Engels1, James R. Cerhan2, Martha S. Linet1, Wendy Cozen3, Joanne S. Colt1, Scott Davis4, Gloria Gridley1, Richard K. Severson5 and Patricia Hartge1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, MD
2 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
3 Department of Preventative Medicine, Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, CA
4 Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA
5 Department of Family Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, MI

Correspondence to Dr. Eric A. Engels, Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, DHHS, 6120 Executive Boulevard, EPS 8010, Rockville, MD 20852 (e-mail: engelse{at}exchange.nih.gov).

In immunosuppressed or autoimmune disease states, disordered immune responses may lead to non-Hodgkin's lymphoma (NHL). In a US population-based case-control study of NHL (1998–2000), the authors collected personal histories of immune-related conditions and use of immune-modulating therapies as well as family histories of autoimmune conditions. The study included 1,321 NHL cases and 1,057 controls; only half received some questionnaire components. NHL was associated with Sjögren's syndrome (odds ratio (OR) = 13, 95% confidence interval (CI): 1.7, 100) and lupus (OR = 4.2, 95% CI: 1.2, 15). Two specific NHL subtypes were strongly associated with Sjögren's syndrome: salivary gland (OR = 290, 95% CI: 33, 2600) and marginal zone (OR = 75, 95% CI: 9.1, 610). NHL was less convincingly associated with receipt of an organ transplant (OR = 2.0, 95% CI: 0.4, 11). Other autoimmune conditions were too rare to evaluate or not associated with NHL. Corticosteroid use was unrelated to NHL (OR = 1.0, 95% CI: 0.8, 1.2), but methotrexate use was marginally associated (OR = 2.3, 95% CI: 0.7, 7.5). Family history of dermatomyositis was associated with NHL (7 cases vs. 0 controls, OR = infinite; two-sided p = 0.02), but dermatomyositis was absent in cases themselves. Family history of remaining conditions was unrelated to NHL. Results suggest that disordered immunity in some immune-related conditions can lead to NHL.

autoimmune diseases; case-control studies; immunosuppression; lymphoma, non-Hodgkin; methotrexate; organ transplantation; risk factors; Sjogren's syndrome


Abbreviations: CI, confidence interval; NHL, non-Hodgkin's lymphoma; OR, odds ratio; SEER, Surveillance, Epidemiology, and End Results; SLE, systemic lupus erythematosus


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