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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3479-3488.
Prepublished online as a Blood First Edition Paper on December 27, 2006February 1, 2007; DOI 10.1182/blood-2006-06-031948.
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Submitted June 27, 2006
Accepted November 20, 2006
Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10,211 cases and 11,905 controls from the InterLymph Consortium
Sophia S Wang*, Susan L Slager, Paul Brennan, Elizabeth A Holly, Silvia De Sanjose, Leslie Bernstein, Paolo Boffetta, James R Cerhan, Marc Maynadie, John J Spinelli, Brian C.H. Chiu, Pierluigi Cocco, Fiona Mensah, Yawei Zhang, Alexandra Nieters, Luigino Dal Maso, Paige M Bracci, Adele Seniori Costantini, Paolo Vineis, Richard K Severson, Eve Roman, Wendy Cozen, Dennis Weisenburger, Scott Davis, Silvia Franceschi, Carlo La Vecchia, Lenka Foretova, Nikolaus Becker, Anthony Staines, Martine Vornanen, Tongzhang Zheng, and Patricia Hartge
Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, Rockville, MD, United States
Dept of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States
Genetic Epidemiology Group, International Agency for Research in Cancer, Lyon, France
Dept of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, United States
Epidemiology & Cancer Registry Unit, Catalan Institute of Oncology, Barcelona, Spain
Dept of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Registre des Hemopathies Malignes de Cote d'Or, Faculte de Medecine de Dijon, Dijon, France
Cancer Control Research Program, British Columbia Cancer Agency, Vancouver, Canada
Dept of Preventive Medicine, Northwestern University Medical School, Chicago, IL, United States
Dept of Public Health, Occupational Health Section, University of Cagliari, Cagliari, Italy
Epidemiology & Genetics Unit, Dept of Health Sciences, University of York, York, United Kingdom
Dept of Epidemiology & Public Health, Yale University School of Medicine, New Haven, CT, United States
Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Epidemiology & Biostatistics Unit, Aviano Cancer Centre, Aviano, Italy
Center for Study & Prevention of Cancer, Unit of Occupational and Environmental Epidemiology, Florence, Italy
Environmental Epidemiology, Imperial College of London, London, United Kingdom
Karmanos Cancer Institute & Dept of Family Medicine, Wayne State University, Detroit, MI, United States
University of Nebraska Medical Center, Omaha, NE, United States
Dept of Epidemiology, School of Public Health & Community Medicine, University of Washington, Seattle, WA, United States
Infections & Cancer Epidemiology, International Agency for Research in Cancer, Lyon, France
Istituto di Ricerche Farmacologiche, & Istituto di Statistica Medica e Biometria, University of Milan, Milan, Italy
Cancer Epidemiology & Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Dept of Public Health, Public Health University College (Dublin), Dublin, Republic of Ireland
Pathology Tampere University Hospital, Tampere, Finland
* Corresponding author; email: wangso{at}mail.nih.gov.
A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10,211 NHL cases and 11,905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (OR) and 95% confidence intervals (CI) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR=1.5;95% CI=1.2-1.9), Hodgkin lymphoma (OR=1.6;95% CI=1.1-2.3), and leukemia (OR=1.4;95% CI=1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR=2.8;95% CI=1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR=1.7;95% CI=1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR=3.0;95% CI=1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.
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