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J Natl Cancer Inst Monogr. 2014 Aug;2014(48):52-65. doi: 10.1093/jncimonographs/lgu011.

Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

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Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (PMB, EAH); Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, Barcelona, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain (YB, SdS); Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, Australia, The Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (JJT); Department of Entomology, The Robert H. Smith Faculty of Agriculture, Koret School of Veterinary Medicine Veterinary Teaching Hospital, Hebrew University of Jerusalem, Rehovot, Israel (OP); Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN (SLS, ADN, JRC); Prince of Wales Clinical School, University of New South Wales, Sydney, Australia (CMV); Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany (NB); Department of Health Studies, University of Chicago, Chicago, IL (BCHC); Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Cagliari, Italy (PC); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (AD); Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany (AN); Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, Heslington, York, UK (EVK, ER); Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (KES); Biological Hematology Unit, CRB Ferdinand Cabanne, University Hospital of Dijon and University of Burgundy, Dijon, France (MM); Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada (JJS); Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden, Department of Oncology and Pathology, Karolinska Institutet, Stockhol



Marginal zone lymphoma (MZL), comprised of nodal, extranodal, and splenic subtypes, accounts for 5%-10% of non-Hodgkin lymphoma cases. A detailed evaluation of the independent effects of risk factors for MZL and its subtypes has not been conducted.


Data were pooled from 1052 MZL cases (extranodal [EMZL] = 633, nodal [NMZL] = 157, splenic [SMZL] = 140) and 13766 controls from 12 case-control studies. Adjusted unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs).


Novel findings for MZL subtypes include increased risk for B-cell activating autoimmune conditions (EMZL OR = 6.40, 95% CI = 4.24 to 9.68; NMZL OR = 7.80, 95% CI = 3.32 to 18.33; SMZL OR = 4.25, 95% CI = 1.49 to 12.14), hepatitis C virus seropositivity (EMZL OR = 5.29, 95% CI = 2.48 to 11.28), self-reported peptic ulcers (EMZL OR = 1.83, 95% CI = 1.35 to 2.49), asthma without other atopy (SMZL OR = 2.28, 95% CI = 1.23 to 4.23), family history of hematologic cancer (EMZL OR = 1.90, 95% CI = 1.37 to 2.62) and of non-Hodgkin lymphoma (NMZL OR = 2.82, 95% CI = 1.33 to 5.98), permanent hairdye use (SMZL OR = 6.59, 95% CI = 1.54 to 28.17), and occupation as a metalworker (NMZL OR = 3.56, 95% CI = 1.67 to 7.58). Reduced risks were observed with consumption of any alcohol (EMZL fourth quartile OR = 0.48, 95% CI = 0.28 to 0.82) and lower consumption of wine (NMZL first to third quartile ORs < 0.45) compared with nondrinkers, and occupation as a teacher (EMZL OR = 0.58, 95% CI = 0.37 to 0.88).


Our results provide new data suggesting etiologic heterogeneity across MZL subtypes although a common risk of MZL associated with B-cell activating autoimmune conditions was found.

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