A review of the data quality and comparability of case-control studies of low-level exposure to benzene in the petroleum industry.

PURPOSE Published case-control studies of risks of leukaemia following low exposures to benzene in the distribution of petroleum (gasoline) have not all identified the same level of risk, but the studies have had differences in cohort inclusion, case determination and availability of occupational and lifestyle data. We reviewed the quality and comparability of the data from three (of four) studies. METHODS Through site visits, discussions with the investigators and reading study reports, we reviewed and audited the methods used for selecting cases and controls, for estimating individual exposures and for analysing and interpreting the data. Case-control comparisons of exposures were examined using customized graphs. RESULTS We found that there were no issues of subject selection, methods or general data quality that were likely to have distorted their internal comparisons; we could not check in detail whether the metric for exposure assessments was the same across the studies; the exposure assessments for the Australian study required the least backward estimation, and the Canadian, which also had fewest cases, the most; evidence of an increased risk at higher exposures in Australia was convincing. CONCLUSIONS The findings are consistent with some effect of benzene at higher lifetime exposures. A proposed pooled analysis should improve quantification of any exposure-response relationship.