Flexible meta-regression to assess the shape of the benzene-leukemia exposure-response curve.
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AbstractBACKGROUND: 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 ppm-years, 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.
CitationEnviron. Health Perspect. 2010, 118 (4):526-532
SponsorsThis work was performed as part of the work package “integrated risk assessment” of the Environmental Cancer Risk, Nutrition and Individual Susceptibility Network of Excellence, operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (FOOD-CT-2005-513943).
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