Acute lymphoid leukemia burden attributable to occupational benzene exposure from 1990-2021: Global patterns, trends, and implications for prevention

Abstract

Abstract Background: Acute lymphoid leukemia (ALL), while primarily a pediatric malignancy, affects adults and is influenced by both genetic and environmental determinants. Benzene, a widely used industrial solvent and established hematotoxicant, has been strongly linked to leukemogenesis through chronic occupational exposure, particularly in the petrochemical, rubber, printing, and transportation industries. Despite regulatory measures, the temporal global burden of ALL attributable to occupational benzene remains inadequately quantified. Methods: A global analysis was conducted to estimate the burden of ALL attributable to occupational benzene exposure from 1990 to 2021, using the standardized global burden of disease 2021 epidemiological modeling. Mortality, years of life lost (YLL), and years lived with disability (YLD) were derived from population-based cancer registries, occupational health surveillance, and mortality databases. Population-attributable fractions were estimated using pooled relative risks from meta-analyses. Age-standardized rates were computed by direct standardization, and temporal trends in absolute counts and rates were assessed using estimated annual percentage change (EAPC) with 95% confidence intervals. Results: Between 1990 and 2021, deaths attributable to occupational benzene increased from 355 (95% UI: 97–595) to 525 (146–896) (EAPC: +1.27%), YLLs from 19,508 (5,319–32,573) to 26,846 (7,607–45,695) (EAPC: +1.04%), and YLDs from 134 (41–240) to 256 (74–471) (EAPC: +2.10%). By SDI level, the highest APC increase in deaths was observed in Low SDI (+3.19%), followed by Low-middle SDI (+2.71%), Middle SDI (+1.34%), and High-middle SDI (+0.46%), whereas High SDI showed a decrease (–0.16%). YLLs followed a similar gradient, with Low SDI (+3.20%), Low-middle SDI (+2.58%), Middle SDI (+1.05%), High-middle SDI (+0.08%), and a decline in High SDI (–0.50%). Regionally, the steepest increases in death counts occurred in Central Sub-Saharan Africa (+3.87%), Andean Latin America (+3.81%), Western Sub-Saharan Africa (+3.72%), Central Latin America (+3.63%), Oceania (+3.24%), Eastern Sub-Saharan Africa (+3.29%), North Africa and Middle East (+2.43%), Caribbean (+2.38%), and Tropical Latin America (+2.31%). Decreases were observed in High-income North America (–0.15%), Central Europe (–1.41%), and Eastern Europe (–1.95%). By age group in 2021, deaths were highest in 20–54 years (416.11; 95% UI: 118.34–710.31), followed by ≥55 years (84.44; 22–143.36), and <20 years (25.33; 7.43–42.07). YLLs in 2021 were greatest in 20–54 years (22,737; 6,490–38,666), then ≥55 years (2,272; 591–3,867), and <20 years (1,836; 538–3,049). By gender, females showed a higher burden over three decades, with APC in deaths (male vs female: +1.15% vs +1.45%), YLLs (+0.93% vs +1.18%), and YLDs (+1.86% vs +2.40%). Conclusion: The global burden of ALL attributable to occupational benzene exposure has increased over the past three decades, with the sharpest growth in low-SDI and certain high-exposure regions, and disproportionately higher increases among females and working-age adults. Strengthened occupational regulations, targeted exposure mitigation, and early detection programs are essential to reduce preventable benzene-related leukemia mortality and disability.