James R Cerhan1, Anne Kricker2, Ora Paltiel2, Christopher R Flowers2, Sophia S Wang2, Alain Monnereau2, Aaron Blair2, Luigino Dal Maso2, Eleanor V Kane2, Alexandra Nieters2, James M Foran2, Lucia Miligi2, Jacqueline Clavel2, Leslie Bernstein2, Nathaniel Rothman2, Susan L Slager2, Joshua N Sampson2, Lindsay M Morton2, Christine F Skibola2. 1. Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JRC, SLS); Sydney School of Public Health, The University of Sydney, Sydney, Australia (AK); Department of Entomology, The Robert H. Smith Faculty of Agriculture, Koret School of Veterinary Medicine Veterinary Teaching Hospital, Hebrew University of Jerusalem, Jerusalem, Israel (OP); Winship Cancer Institute, Emory University, Atlanta, GA (CRF); Department of Cancer Etiology, Beckman Research Institute of the City of Hope, Duarte, CA (SSW, LB); Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Group, F-94805, and Univ Paris Sud, UMRS 1018, F-94805, Villejuif, France (AM, JC); Registry of Hematological Malignancies in Gironde, Bergonié Institute, Bordeaux, France (AM); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (AB, NR, JNS, LMM); Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy (LDM); Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, UK (EVK); Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany (AN); Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL (JMF); Unit of Occupational and Environmental Epidemiology, Cancer Prevention and Research Institute ISPO Florence, Florence, Italy (LM); Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (CFS). cerhan.james@mayo.edu. 2. Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JRC, SLS); Sydney School of Public Health, The University of Sydney, Sydney, Australia (AK); Department of Entomology, The Robert H. Smith Faculty of Agriculture, Koret School of Veterinary Medicine Veterinary Teaching Hospital, Hebrew University of Jerusalem, Jerusalem, Israel (OP); Winship Cancer Institute, Emory University, Atlanta, GA (CRF); Department of Cancer Etiology, Beckman Research Institute of the City of Hope, Duarte, CA (SSW, LB); Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Group, F-94805, and Univ Paris Sud, UMRS 1018, F-94805, Villejuif, France (AM, JC); Registry of Hematological Malignancies in Gironde, Bergonié Institute, Bordeaux, France (AM); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (AB, NR, JNS, LMM); Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy (LDM); Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, UK (EVK); Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany (AN); Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL (JMF); Unit of Occupational and Environmental Epidemiology, Cancer Prevention and Research Institute ISPO Florence, Florence, Italy (LM); Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (CFS).
Abstract
BACKGROUND: Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown. METHODS: In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites. RESULTS: DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m(2)), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for <18.5 vs 18.5 to 22.4 kg/m(2)), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for >400 kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs; inflammatory bowel disease was associated with gastrointestinal DLBCL; and farming and hair dye use were associated with mediastinal DLBCL. CONCLUSION: Our results support a complex and multifactorial etiology for DLBCL with some variation in risk observed by sex and anatomical site. Published by Oxford University Press 2014.
BACKGROUND: Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown. METHODS: In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites. RESULTS: DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m(2)), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for <18.5 vs 18.5 to 22.4 kg/m(2)), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for >400 kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs; inflammatory bowel disease was associated with gastrointestinal DLBCL; and farming and hair dye use were associated with mediastinal DLBCL. CONCLUSION: Our results support a complex and multifactorial etiology for DLBCL with some variation in risk observed by sex and anatomical site. Published by Oxford University Press 2014.
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