title: A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies.
abstract: OBJECTIVE
  Establishing a causal relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and risk of specific lymphoid cancers, including non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM), would be useful for risk assessment.
  
  
  METHODS
  This article systematically and critically reviews epidemiologic studies of the association between exposure to TCDD or TCDD-contaminated herbicides and risk of lymphoid malignancies. These include studies of military, industrial, accidental environmental, and general environmental exposure to Agent Orange or TCDD.
  
  
  RESULTS
  Collectively, the epidemiologic evidence from industrial cohorts suggests a positive association with NHL mortality, but results are not consistent across other studies, a clear exposure-response gradient is not evident, and data are insufficient to conclude that the association is causal. Furthermore, available studies provide little information on NHL incidence or specific NHL subtypes. Epidemiologic studies do not show an association of TCDD exposure with HL, whereas the indication of a positive association with MM in a limited number of studies, but not others, remains to be confirmed in additional research. Exposure classification error and small numbers are important limitations of the available epidemiologic studies.
  
  
  CONCLUSIONS
  Overall, a causal effect of TCDD on NHL, HL, MM, or subtypes of these lymphoid malignancies has not been established.
authors: Health Sciences Practice, Exponent, Inc., Menlo Park, CA; Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA. Electronic address: echang@exponent.com.
authors: Ellen T
authors: ET
authors: Chang
authors: Institute for Translational Epidemiology and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Paolo
authors: P
authors: Boffetta
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors: Hans-Olov
authors: HO
authors: Adami
authors: Health Sciences Practice, Exponent, Inc., Menlo Park, CA.
authors: Jack S
authors: JS
authors: Mandel
mesh_terms: D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000075182:Agent Orange; D006540:Herbicides / Q000633:toxicity*; D006689:Hodgkin Disease / Q000139:chemically induced; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced; D008232:Lymphoproliferative Disorders / Q000139:chemically induced*; D009101:Multiple Myeloma / Q000139:chemically induced; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
chemical_list: D006540:Herbicides; D000072317:Polychlorinated Dibenzodioxins; D015084:2,4-Dichlorophenoxyacetic Acid; D000075182:Agent Orange; D015085:2,4,5-Trichlorophenoxyacetic Acid
keywords: Agent Orange; Epidemiology; Lymphoma; Lymphoma, Hodgkin; Lymphoma, Non-Hodgkin; Multiple myeloma; Tetrachlorodibenzodioxin