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American Journal of Epidemiology Advance Access published online on October 26, 2005
American Journal of Epidemiology, 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.
Received March 4, 2005
Accepted July 18, 2005

ORIGINAL CONTRIBUTIONS

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

Eric A. Engels 1*, James R. Cerhan 2, Martha S. Linet 1, Wendy Cozen 3, Joanne S. Colt 1, Scott Davis 4, Gloria Gridley 1, Richard K. Severson 5, and Patricia Hartge 1

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

* To whom correspondence should be addressed.
Eric A. Engels, E-mail: engelse{at}exchange.nih.gov


  Abstract

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.

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