Flexible meta-regression to assess the shape of the benzene--leukemia exposure--response curve.

Background: Previous evaluations of the shape of the benzene-leukemia exposure-response curve (ERC) were based on a single set or on small sets of human occupational studies. Integrating evidence from all available studies that are of sufficient quality combined with flexible meta-regression models...

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Published in:Environmental Health Perspectives Vol. 118; no. 4; pp. 526 - 533
Main Authors: Vlaanderen J, Portengen L, Rothman N, Lan Q, Kromhout H, Vermeulen R
Format: meta analysis research systematic review tables/charts Journal Article
Published: National Institute of Environmental Health Sciences Apr2010
Online Access:View this record in EBSCOhost
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      dt: Apr2010
      vid: 118
      iid: 4
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      pub: National Institute of Environmental Health Sciences
      place: Research Triangle Park, North Carolina
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        105169264
        2010620798
        10.1289/ehp.0901127
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        atl: Flexible meta-regression to assess the shape of the benzene--leukemia exposure--response curve.
      aug:
        au:
          Vlaanderen J
          Portengen L
          Rothman N
          Lan Q
          Kromhout H
          Vermeulen R
        affil: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
      sug:
        subj:
          Benzene Derivatives Adverse Effects
          Dose-Response Relationship
          Environmental Exposure
          Leukemia Risk Factors
          Confidence Intervals
          Data Analysis Software
          Human
          Meta Analysis
          Odds Ratio
          PubMed
      ab: Background: Previous evaluations of the shape of the benzene-leukemia exposure-response curve (ERC) were based on a single set or on small sets of human occupational studies. Integrating evidence from all available studies that are of sufficient quality combined with flexible meta-regression models is likely to provide better insight into the functional relation between benzene exposure and risk of leukemia. Objectives: We used natural splines in a flexible meta-regression method to assess the shape of the benzene-leukemia ERC. Methods: We fitted meta-regression models to 30 aggregated risk estimates extracted from nine human observational studies and performed sensitivity analyses to assess the impact of a priori assessed study characteristics on the predicted ERC. Results: The natural spline showed a supralinear shape at cumulative exposures less than 100 ppmyears, although this model fitted the data only marginally better than a linear model (p = 0.06). Stratification based on study design and jackknifing indicated that the cohort studies had a considerable impact on the shape of the ERC at high exposure levels (> 100 ppm-years) but that predicted risks for the low exposure range (< 50 ppm-years) were robust. Conclusions: Although limited by the small number of studies and the large heterogeneity between studies, the inclusion of all studies of sufficient quality combined with a flexible meta-regression method provides the most comprehensive evaluation of the benzene-leukemia ERC to date. The natural spline based on all data indicates a significantly increased risk of leukemia [relative risk (RR) = 1.14; 95% confidence interval (CI), 1.04-1.26] at an exposure level as low as 10 ppm-years.
      pubtype: Academic Journal
      doctype:
        meta analysis
        research
        systematic review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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