Associations between benzene exposure and allergic rhinitis risk and survival in older adults: the mediating role of biological aging and the moderating influence of genetic susceptibility

Allergic rhinitis (AR) is an immune-mediated airway disorder increasingly linked to environmental pollution. This study examined the long-term association of benzene exposure with AR and all-cause mortality in older adults and explored the potential mediating role of biological aging and modification by genetic susceptibility. Data from 76,183 UK Biobank participants aged ≥ 65 years at baseline were linked with annual residential benzene estimates (2006–2020) from the DEFRA 1 km × 1 km model. Cox proportional hazards models evaluated associations with AR incidence and mortality, and restricted cubic splines assessed nonlinearity, and multistate models characterized transitions between AR and death. Four biological aging markers-PhenoAge, Klemera-Doubal biological age (KDM), Homeostatic Dysregulation (HD), and Accelerated Biological Aging (ABA)-were incorporated into bootstrap mediation models. Genetic risk was quantified using a polygenic risk score (PRS) derived from 35 genome-wide significant SNPs. Over median follow-ups of 13.3 years for AR and 14.8 years for mortality, 756 AR cases and 17,963 deaths were recorded. Each interquartile range (IQR, 0.151 μg/m 3 ) increase in benzene concentration was associated with higher risks of AR (HR = 1.44, 95% CI 1.31–1.57) and mortality (HR = 1.21, 95% CI 1.19–1.23). Multistate analyses associated higher benzene exposure with transitions from an AR-free state to incident AR or death, but not from incident AR to death. Thresholds were identified at 0.255 μg/m 3 for AR and 0.277 μg/m 3 for mortality. Biological aging partially mediated these associations (mediation proportion up to 15.2%), and participants in the highest PRS tertile had a higher AR risk than those in the lowest tertile (HR = 1.54, 95% CI 1.29–1.85). Sensitivity analyses supported the robustness of the findings. Chronic low-level benzene exposure was associated with higher risks of AR and all-cause mortality in older adults. Biological aging may partly mediate these associations, with genetic susceptibility further modifying AR risk through positive additive interaction.