title: Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study.
abstract: Evidence suggests a largely environmental component to non-Hodgkin's lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined.
  
  
  
  The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers.
  
  
  
  The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p < 0.05) in median exposure levels between cases and controls for any of the investigated exposures. However under a multivariate model PCB138, PCB153, HCB and DDE displayed significant inverse trends (Wald test p-value <0.05). Under stratified analyses these were determined to be driven by males and by the Diffuse Large B-Cell Lymphoma subtype. When considering those in the highest levels of exposure (>90thpercentile) the association was null for all POPs CONCLUSION: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. hprke@channing.harvard.edu.|Department of Epidemiology and Biostatistics, Imperial College London, London, UK. hprke@channing.harvard.edu.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Kelly
authors.affiliation: National Institute for Health and Welfare Chemicals and Health Unit, Neulanen Research Centre, Neulaniementie 4, FI-70210, Kuopio, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kiviranta
authors.affiliation: Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ingvar A
authors.initials: IA
authors.lastname: Bergdahl
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Johansson
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Pharmaceutical Chemistry and Biotechnology, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Botsivali
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK.|HuGeF Foundation, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Pharmaceutical Chemistry and Biotechnology, Athens, Greece.
authors.forename: Soterios A
authors.initials: SA
authors.lastname: Kyrtopoulos
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Chadeau-Hyam
mesh_terms: D001822:Body Burden; D016022:Case-Control Studies; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood*; D007558:Italy / Q000453:epidemiology; D016393:Lymphoma, B-Cell / Q000097:blood / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated
keywords: DDE; EnviroGenoMarkers; HCB; Non Hodgkin lymphoma; Organochlorines; Polychlorinated biphenyls