1. BACKGROUND Benzene is a known carcinogen. Occupational exposure to benzene is an established risk factor for leukaemia. Less is known about the effects of long-term exposure to low doses in the environment. Vulnerable groups, such as children, may be at risk. RESULTS STUDY DESIGN Ecological study on wards within the area of London bounded by the M25 orbital motorway. Leukaemia incidences in children aged 0-14 between 1985 and 2001 obtained from national cancer register. Postcode-level benzene concentrations for two periods (1991-1996 and 1997-2002) estimated using an air dispersion model (ADMS- Urban) from road, traffic, emissions and meteorological data. Annual incidence (peak in Inner London, 1989-1990) Smoothed SMRs across London Leukaemia data Benzene data Benzene-leukaemia association Slight increasing trend in smoothed SMRs with benzene, by ward / time period Big decrease in traffic-related benzene since 1990 (cleaner engines, catalytic converters, cleaner petrol) Peaks in traffic-related benzene along roads and in inner London. STATISTICAL MODELS Model 1: Poisson model for standardised incidence of leukaemia y ij in area i and time period j, in terms of mean benzene exposure x ij. y ij ~ Poisson(E ij  ij ), log(  ij ) = α + β x ij Elaborate this basic model, step by step, to account for various sources of potential bias and uncertainty: Model 2: Between area heterogeneity in baseline risks log(  ij ) = α + β x ij + H i, with H i ~ N(0, σ 2 H ) Model 3: Between area heterogeneity (spatially correlated) log(  ij ) = α + β x ij + S i + H i, with S i ~ CAR(σ 2 s ) Model 4: Ecological bias correction. Account for the within-area variance v ij of exposure. log(  ij ) = α + β x ij + S i + H i + 0.5 β 2 v ij Model 5: Relative risks varying between areas log(  ij ) = α + β x ij + S i + H i + 0.5 (B i + β) 2 v ij + B i x ij, with B i ~ CAR(σ 2 B ) Model 6: Exposure measurement error. log(  ij ) = α + β x ij * + S i + H i + 0.5 (B i + β) 2 v ij * + B i x ij *, with x ij * ~ N(  ij x, σ 2 ij x ) and v ij * ~ Gamma(a ij v, b ij v ) Various plausible sizes of unbiased measurement error considered. IMPLEMENTATION Bayesian hierarchical model MCMC simulation from posterior distributions using WinBUGS Graph of most complex model Estimated relative risks for benzene RR of 1.33 for 1 unit of benzene (cube root  g/m 3 ) implies: 15% reduction in risk associated with the reduction in mean benzene concentration from the 1991-1996 to 1997-2002 periods 7% increase in risk from a low pollution postcode (10% quantile of benzene concentration in London, 1997-2002) to a high one (90% quantile) DIC suggests little difference in fit between models 2-6. Conclusions robust to ecological bias (within-area exposure variability, model 4) and, similarly, to exposure measurement error and early-period extrapolation (model 6). 95% probability interval for area-level residual relative risks shortens from (0.91, 1.29) (model 4) to (0.99, 1.16) after accounting for varying benzene RRs (model 5). Residual relative risks of leukaemia (model 5) are spatially correlated, suggesting presence of unaccounted-for area-level risk factors. Model fitted to two datasets Exposure and incidence 1991-2002. Exposure and incidence 1985-2002, with exposures in 1985-1990 estimated by extrapolation: Uncertainty about this extrapolation incorporated in measurement error model (6) WORK IN PROGRESS Investigate other potential risk factors for childhood leukaemia: Proximity to power lines Proximity to mobile telephone masts Population “mixing” (instability). Other traffic-related pollutants? These may confound the benzene effect. Investigate effect on acute myelogenous leukaemia (most strongly linked with occupational benzene exposure) Threshold effect for low-level benzene exposure? Emissions policy Air Quality Strategy for the UK (2000): annual mean benzene of 3.24  g/m 3 (1 ppb), to be achieved by end of 2005. Failed for 3% of postcodes in London in 1996-2001. Achieved for all postcodes in London in 1997-2002. BACKGROUND Benzene is a known carcinogen. Occupational exposure to benzene is an established risk factor for leukaemia. Less is known about the effects of long-term exposure to low doses in the environment. Vulnerable groups, such as children, may be at risk. Hierarchical modelling of traffic-related benzene and childhood leukaemia in London Dr. Christopher Jackson, Prof. Nicky Best, Dr. Kees De Hoogh and Prof. Sylvia Richardson Department of Epidemiology and Public Health, Imperial College, London