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American Journal of Epidemiology Advance Access originally published online on March 4, 2008
American Journal of Epidemiology 2008 167(9):1081-1089; doi:10.1093/aje/kwn004
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Smoking and Lymphoma Risk in the European Prospective Investigation into Cancer and Nutrition

Alexandra Nieters1, Sabine Rohrmann1, Nikolaus Becker1, Jakob Linseisen1, Thomas Ruediger2, Kim Overvad3, Anne Tjønneland4, Anja Olsen4, Naomi E. Allen5, Ruth C. Travis5, Sheila Bingham6, Kay-Tee Khaw7, Eva Ardanaz8, M. L. Redondo9, Mikel Basterrechea10, Carmen Martinez11, María-José Tormo12, Stefano Rosso13, Giovanna Tagliabue14, Giovanna Masala15, Amalia Mattiello16, Rosario Tumino17, Heiner Boeing18, Manuela Bergmann18, Rudolf Kaaks1, Antonia Trichopoulou19, Dimitrios Trichopoulos20, Petra H. Peeters21, Bas Bueno-de-Mesquita22, Paolo Boffetta23, Paul Brennan24, Pietro Ferrari25, David Neasham26, Eiliv Lund27, Göran Berglund28, Jonas Manjer29, Göran Hallmans30, Ingegerd Johansson31, Paolo Vineis32 and Elio Riboli32

1 Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
2 Pathologisches Institut, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
3 Department of Clinical Epidemiology, Aalborg Hospital and Aarhus University Hospital, Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark
4 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
5 Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
6 Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom
7 Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom
8 Public Health Institute of Navarra, Pamplona, Spain
9 Public Health and Health Planning Directorate, Asturias, Spain
10 Public Health Division of Gipuzkoa, San Sebastian, Spain
11 Escuela Andaluza de Salud Publica, Granada, Spain
12 Epidemiology Department, Murcia Health Council, Murcia, Spain
13 CPO Piemonte, Torino, Italy
14 Instituto Nationale Tumori, Milano, Italy
15 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy
16 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
17 Cancer Registry Azienda Ospedaliera "Civile M. P. Arezzo" Ragusa, Ragusa, Italy
18 German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
19 Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
20 Hellenic Health Foundation, Athens, Greece
21 Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands
22 Centre for Nutrition and Health, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
23 Gene-Environment Epidemiology Group, International Agency for Research on Cancer, Lyon, France
24 Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
25 Nutrition and Hormones Group, International Agency for Research on Cancer, Lyon, France
26 Department of Epidemiology & Public Health Medicine, Imperial College, London, United Kingdom
27 Institute of Community Medicine, University of Tromso, Tromso, Norway
28 Department of Clinical Sciences, Malmö University Hospital, Malmö, Sweden
29 Department of Surgery, Malmö University Hospital, Malmö, Sweden
30 Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden
31 Department of Odontology, Cariology, Umeå University, Umeå, Sweden
32 Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom

Correspondence to Dr. Alexandra Nieters, Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (e-mail: a.nieters{at}dkfz.de).

Received for publication June 11, 2007. Accepted for publication January 3, 2008.

Lymphomas are one of the few cancers that have been increasing in incidence over the past decades. So far, only a few established risk factors have been identified, including immunosuppression and viral infections. Recent evidence suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may affect risk differently, depending on the lymphoma entity. The European Prospective Investigation into Cancer and Nutrition was used to study the role of smoking in the etiology of lymphomas and individual subtypes within a prospective study. Information on baseline and lifetime tobacco smoking by 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified. Relative risk for smokers at recruitment was more than twofold higher for Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In this prospective study, smoking appeared to increase Hodgkin's lymphoma risk consistently in both genders, whereas B-cell non–Hodgkin's lymphoma risk was not associated. Future analysis should involve viral biomarkers and genetic susceptibility markers to elucidate potential mechanisms of smoking-induced carcinogenesis, particularly for Hodgkin's lymphoma.

lymphoma; prospective studies; risk factors; smoking

Abbreviations: CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; EPIC, European Prospective Investigation into Cancer and Nutrition; HR, hazard ratio; ICD-O-2, International Classification of Diseases for Oncology, second edition


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