Exposure to potentially toxic elements and gallbladder cancer risk: An ecological study from Bihar, India

Gallbladder cancer (GBC) is an aggressive malignancy with marked geographic variation, including elevated incidence rates in parts of South Asia. However, the causes of this heterogeneity and the etiology of GBC remain largely unclear. To explore potential environmental contributors, this study examined the possible role of potentially toxic elements (PTEs) in environmental co-exposure using rural Bihar, India, as a case study. We utilized geographically weighted regression coefficients derived from 8460 GBC cases. These coefficients represent locally varying associations between GBC incidence and subdistrict-level socio-environmental factors. We specifically used estimated coefficients for well- and canal-irrigated area coverage as proxies for environmental exposure through agricultural inputs. The local coefficients were linked to subdistrict-level soil geochemistry data comprising concentrations of multiple PTEs. Seven elements (As, Cr, Ni, Pb, Cu, Zn, and U) were examined as explanatory variables. The analysis was conducted as a subdistrict-level ecological study across 112 subdistricts. The results showed consistent and strong associations between uranium (U) and irrigation-related GBC risk. The model including interaction terms identified a positive (synergistic) effect between U and Ni. The regression model incorporating interaction terms demonstrated reasonable explanatory power (R² = 0.412; adjusted R² = 0.33) and was generally consistent with existing biological and medical evidence, supporting the plausibility of the observed associations. The main associations were reassessed using Poisson regression models for subdistrict-level GBC counts and were broadly supported. By integrating spatially varying epidemiological associations with environmental geochemical data, this study provides new insights into possible exposure pathways underlying spatial disparities in GBC incidence.