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

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BlankBlood First Edition Paper, prepublished online December 27, 2006; DOI

10.1182/blood-2006-06-031948.

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*, L Slager, Brennan, A Holly, Silvia De

Sanjose, Bernstein, Paolo Boffetta, R Cerhan, Marc Maynadie, J

Spinelli, C.H. Chiu, Pierluigi Cocco, Fionah Mensah, Yawei Zhang,

andra Nieters, Luigino Dal Maso, Paige M Bracci, Adele Seniori Costantini,

Paolo Vineis, K Severson, Eve Roman, Cozen, Dennis Weisenburger,

, Silvia Franceschi, Carlo La Vecchia, Lenka Foretova, Nikolaus

Becker, Staines, e Vornanen, Tongzhang Zheng, and 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, 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 " Negri " , & Instituto 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@... .

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.