Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

BACKGROUND: The use of occupational cohort studies to assess the association of benzene and lymphoma is complicated by problems with exposure misclassification, outcome classification, and low statistical power. OBJECTIVE: We performed meta-analyses of occupational cohort studies for five different lymphoma categories: Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). DATA EXTRACTION: We assessed three study quality dimensions to evaluate the impact of study quality variations on meta-relative risks (mRRs): stratification by the year of start of follow-up, stratification by the strength of the reported acute myelogenous leukemia association, and stratification by the quality of benzene exposure assessment. DATA SYNTHESIS: mRRs for MM, ALL, and CLL increased with increasing study quality, regardless of the study quality dimension. mRRs for NHL also increased with increasing study quality, although this effect was less pronounced. We observed no association between occupational benzene exposure and HL. CONCLUSIONS: Our meta-analysis provides support for an association between occupational benzene exposure and risk of MM, ALL, and CLL. The evidence for an association with NHL is less clear, but this is likely complicated by the etiologic heterogeneity of this group of diseases. Further consideration of the association between benzene and NHL will require delineation of risks by NHL subtype.