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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4029-4038.
Prepublished online as a Blood First Edition Paper on February 8, 2008; DOI 10.1182/blood-2007-10-119974.
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Submitted October 24, 2007
Accepted January 25, 2008
Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
Karin Ekstrom Smedby*, Claire M Vajdic, Michael Falster, Eric A Engels, Otoniel Martinez-Maza, Jennifer Turner, Henrik Hjalgrim, Paolo Vineis, Adele Seniori Costantini, Paige M Bracci, Elizabeth A Holly, Eleanor Willett, John J Spinelli, Carlo La Vecchia, Tongzhang Zheng, Nikolaus Becker, Silvia De Sanjose, Brian C.-H. Chiu, Luigino Dal Maso, Pierluigi Cocco, Marc Maynadie, Lenka Foretova, Anthony Staines, Paul Brennan, Scott Davis, Richard Severson, James R Cerhan, Elizabeth C Breen, Brenda Birmann, Andrew E Grulich, and Wendy Cozen
Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, United States
Department of Microbiology, Immunology and Molecular Genetic, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
Department of Anatomical Pathology, St. Vincent's Hospital, Sydney, Australia
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Environmental Epidemiology, Imperial College London, London, United Kingdom
Epidemiology Unit, Center for Study and Prevention of Cancer, Istituto Scientifico Regione Toscana, Florence, Italy
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States
Epidemiology & Genetics Unit, University of York, York, United Kingdom
Cancer Control Research Program, BC Cancer Agency, Vancouver, Canada
Istituto di Ricerche Farmacologiche "Mario Negri" and Istituto di Statistica Medica e Biometria, Universita degli Studi di Milano, Milano, Italy
Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT, United States
Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Epidemiologia i Registre del Cancer, Institut Catala d' Oncologia, Barcelona, Spain
Department of Preventive Medicine, Northwestern University Medical School, Chicago, IL, United States
Epidemiology and Biostatistics Unit, Aviano Cancer Centre, Aviano, Italy
Department of Public Health, Occupational Health Section, University of Cagliari, Cagliari, Italy
Registry of Hematological Malignacies of Cote d'Or, Dijon, France
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
School of Nursing, Dublin City University, Dublin, Republic of Ireland
International Agency for Research on Cancer, Lyon, France
Fred Hutchinson Cancer Research Centre & School of Public Health and Community Medicine, University of Washington, Seattle, WA, United States
Department of Family Medicine and Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, United States
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
Keck School of Medicine, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States
* Corresponding author; email: karin.ekstrom.smedby{at}ki.se.
Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29,423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren's syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR 996, 95% CI 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL, and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type-1 diabetes, sarcoidosis, pernicious anemia and multiple sclerosis were not associated with risk of NHL or subtypes. We conclude that specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
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