title: Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition.
abstract: Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive ≥0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found.
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg, 79108 Freiburg, Germany, Institute of Laboratory Medicine, Clinical Chemistry and Medical Diagnostics, University Hospital Leipzig 04103, Leipzig, Germany, Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany, Julius Center, University Medical Center Utrecht, 3508 Utrecht, The Netherlands, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), 3508 Utrecht University, Utrecht, The Netherlands, Department of Public Health, Section of Epidemiology, Aarhus University, 8000 Aarhus, Denmark, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany, Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, 115 27 Greece, Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115 USA, Bureau of Epidemiologic Research, Academy of Athens, 115 27 Athens, Greece, Hellenic Health Foundation, Athens, Greece, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50141 Florence, Italy, Dipartamento di Medicina Clinica e Chirurgia, Federico II University, 80138 Naples, Italy, Cancer Registry and Histopathology Unit, 'Civile M.P.Arezzo' Hospital, ASP Ragusa, Italy, Center for Cancer Prevention (CPO-Piemonte), Turin, Italy, Human Genetics Foundation, 10126 Turin, Italy, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands, Department of Gastroenterology and Hepatology, University Medical Center, 3508 GA Utrecht, The Netherlands, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic Unive
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg, 79108 Freiburg, Germany, Institute of Laboratory Medicine, Clinical Chemistry and Medical Diagnostics, University Hospital Leipzig 04103, Leipzig, Germany, Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany, Julius Center, University Medical Center Utrecht, 3508 Utrecht, The Netherlands, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), 3508 Utrecht University, Utrecht, The Netherlands, Department of Public Health, Section of Epidemiology, Aarhus University, 8000 Aarhus, Denmark, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany, Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, 115 27 Greece, Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115 USA, Bureau of Epidemiologic Research, Academy of Athens, 115 27 Athens, Greece, Hellenic Health Foundation, Athens, Greece, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50141 Florence, Italy, Dipartamento di Medicina Clinica e Chirurgia, Federico II University, 80138 Naples, Italy, Cancer Registry and Histopathology Unit, 'Civile M.P.Arezzo' Hospital, ASP Ragusa, Italy, Center for Cancer Prevention (CPO-Piemonte), Turin, Italy, Human Genetics Foundation, 10126 Turin, Italy, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands, Department of Gastroenterology and Hepatology, University Medical Center, 3508 GA Utrecht, The Netherlands, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic Unive
authors.forename: Anna
authors.initials: A
authors.lastname: Łuczyńska
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg, 79108 Freiburg, Germany.
authors.forename: Susen
authors.initials: S
authors.lastname: Becker
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Medical Diagnostics, University Hospital Leipzig 04103, Leipzig, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, 69120 Heidelberg, Germany, Julius Center, University Medical Center Utrecht, 3508 Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), 3508 Utrecht University, Utrecht, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Department of Public Health, Section of Epidemiology, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.affiliation: Department of Public Health, Section of Epidemiology, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany, Bureau of Epidemiologic Research, Academy of Athens, 115 27 Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50141 Florence, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Dipartamento di Medicina Clinica e Chirurgia, Federico II University, 80138 Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Cancer Registry and Histopathology Unit, 'Civile M.P.Arezzo' Hospital, ASP Ragusa, Italy, Center for Cancer Prevention (CPO-Piemonte), Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Human Genetics Foundation, 10126 Turin, Italy, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Human Genetics Foundation, 10126 Turin, Italy, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Jeurnink
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Program on Genetic Research, Folkhälsan Research Center, Samfundet Folkhälsan, University of Helsinki, 00014, Helsinki, Finland, CIBER Epidemiología y Salud Pública, 08003 Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: Program on Genetic Research, Folkhälsan Research Center, Samfundet Folkhälsan, University of Helsinki, 00014, Helsinki, Finland, Navarre Public Health Institute, E-31003 Pamplona, Spain.
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: Program on Genetic Research, Folkhälsan Research Center, Samfundet Folkhälsan, University of Helsinki, 00014, Helsinki, Finland, Department of Epidemiology, Murcia Regional Health Council, 30008 Murcia, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: School of Public Health, 18011Granada, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Sánchez
authors.affiliation: Public Health Directorate, 33009 Asturias, Spain.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: Department of Oncology, Skåne University Hospital.
authors.forename: Salma
authors.initials: S
authors.lastname: Butt
authors.affiliation: and Department of Clinical Sciences, Lund University, 22100 Lund, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
authors.affiliation: and Department of Clinical Sciences, Lund University, 22100 Lund, Sweden.
authors.forename: Florentin
authors.initials: F
authors.lastname: Späth
authors.affiliation: International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Department of Surgery, Lund University, Skåne University Hospital, 20502 Malmö, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, 115 27 Greece, Department of Radiation Sciences, Oncology Umeå University, 901 85 Umeå, Sweden.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Kelly
authors.affiliation: International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Center for Cancer Prevention (CPO-Piemonte), Turin, Italy, Department of Radiation Sciences, Oncology Umeå University, 901 85 Umeå, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Medical Diagnostics, University Hospital Leipzig 04103, Leipzig, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D008223:Lymphoma / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D007073:Immunoglobulin E