Global patterns and inequities in environmental exposure-associated leukemia mortality by sex and socio-demographic index: A 32-year global analysis

Abstract

Abstract Introduction: Leukemia, a malignant neoplasm of the hematopoietic system, remains a substantial contributor to global cancer mortality. Environmental and occupational exposures, including ionizing radiation, chemicals such as benzene, and other carcinogens, play a recognized role in its etiology, particularly in low- and middle-resource settings where regulatory controls and public health interventions may be less robust. This study aimed to provide a comprehensive evaluation of global, sex- and income-stratified trends in leukemia mortality attributed to environmental risk factors. Methods: This analysis utilized estimates from the Global Burden of Disease database (GBD) 2021 study, focusing on deaths due to leukemia with environmental and occupational risks as the attributable risk factor. Age-adjusted mortality rates were extracted for the years 1990 through 2021, stratified by sex and by SDI region (High, High- middle, Middle, Low-middle, and Low SDI), as well as globally. Average annual percentage change (AAPC) with 95% CI was estimated based on joinpoint regression models. Statistical significance of AAPC was assessed via p-values. Additionally, univariate regression analysis evaluated the linear association between time and regional mortality rates, reporting slope, r-squared (r²), and p-values. Results: AAMRs due to environmental and occupational risk factors for leukemia showed marked variation across SDI regions and sexes. High SDI regions consistently exhibited the lowest AAMRs for both sexes, while Low and Low-middle SDI regions experienced considerably higher burdens. Across regions, AAMRs for males generally exceeded those for females, reflecting established sex-based disparities in leukemia mortality. Globally, environmentally associated leukemia mortality rates showed a modest yet statistically significant decline from 1990 to 2021 for both sexes (AAPC: -0.30; 95% CI: -0.38, -0.22), with a more pronounced reduction for males (AAPC: -0.39; 95% CI: -0.46, -0.32) than females (AAPC: -0.18; 95% CI: -0.27, -0.09). High SDI regions demonstrated the steepest downward trend (Both sexes AAPC: -0.76; 95% CI: -0.80, -0.72), and declines were significant for both males and females. In contrast, Low-middle SDI regions displayed an alarming increase (Both sexes AAPC: 0.53; 95% CI: 0.43, 0.64), especially among females (AAPC: 0.94; 95% CI: 0.82, 1.07). Low SDI regions also saw a mild increase overall (Both sexes AAPC 0.10; 95% CI: 0.02, 0.18), with a particular rise in females (AAPC: 0.38; 95% CI 0.26, 0.50). In High-middle and Middle SDI regions, AAMRs declined, but less steeply than in the High SDI group, with Middle SDI both sexes AAPC: -0.22 (95% CI: -0.29, - 0.15). Univariate regression analysis highlighted a strong association between time and decreasing leukemia mortality in High SDI regions (slope: -0.000208, r²: 0.51, p<0.0001), while in Low and Low-middle SDI regions, changes over time were minimal and not statistically significant. Conclusion: This global assessment demonstrates persistent and, in some cases, worsening disparities in leukemia mortality attributable to environmental exposures across lines of income and sex. The rapid and consistent decline in AAMR and AAPC observed in High SDI countries likely reflects the success of environmental regulation, occupational safety standards, and healthcare system improvements. In stark contrast, Low and Low-middle SDI regions not only failed to demonstrate meaningful reductions but, in some cases, experienced rising trends in mortality, especially among females, suggesting widening gaps in environmental health equity. These findings highlight that progress made in high-income settings has not generalized to low-resource environments, where populations may lack adequate exposure protections, public health infrastructure, and access to early detection or effective cancer care. Going forward, targeted interventions to mitigate environmental and occupational hazards, strengthen health systems, and ensure equitable implementation of protective policies are urgently required to address these global disparities in leukemia deaths. These efforts must prioritize the most affected SDI regions and pay keen attention to the rising vulnerability of women in low- and middle-income countries, recognizing the intersectionality of environmental injustice and gender inequity.