Ecological regression analysis of environmental benzene exposure and childhood leukaemia: sensitivity to data inaccuracies, geographical scale and ecological bias

Benzene is classified as a group 1 human carcinogen by the International Agency for Research on Cancer, and it is now accepted that occupational exposure is associated with an increased risk of various leukaemias. However, occupational exposure accounts for less than 1% of all benzene exposures, the major sources being cigarette smoking and vehicle exhaust emissions. Whether such low level exposures to environmental benzene are also associated with the risk of leukaemia is currently not known. In this study, we investigate the relationship between benzene emissions arising from outdoor sources (predominantly road traffic and petrol stations) and the incidence of childhood leukaemia in Greater London. An ecological design was used because of the rarity of the disease, the difficulty of obtaining individual level measurements of benzene exposure and the availability of data. However, some methodological difficulties were encountered, including problems of case registration errors, the choice of geographical areas for analysis, exposure measurement errors and ecological bias. We use a Bayesian hierarchical modelling framework to address these issues, and we investigate the sensitivity of our inference to various modelling assumptions.