Geographic clustering of renal cell carcinoma in West Virginia counties with historical perfluorooctanoic acid (PFOA) exposure.

e16525 Background: Perfluorooctanoic acid (PFOA), a persistent per- and polyfluoroalkyl substance (PFAS), has contaminated multiple regions of West Virginia (WV) through historical industrial activity. We evaluated whether WV counties with documented PFOA exposure demonstrate increased renal cell carcinoma (RCC) prevalence compared with statewide rates and whether similar patterns are observed for other malignancies. Methods: We conducted a county-level ecological analysis of all 55 WV counties using Epic electronic health record–derived cancer data from 2015–2025. RCC cases included all histologic subtypes of renal cell carcinoma and explicitly excluded urothelial malignancies of the renal pelvis. County-specific prevalence rates were calculated using county population denominators. Crude relative risk (RR) estimates with 95% confidence intervals (CI) were calculated relative to statewide RCC prevalence using Poisson-based methods. Lung, colorectal, prostate, thyroid, and bladder cancers were analyzed as comparators to assess cancer specificity, with bladder cancer included as a urothelial malignancy distinct from renal parenchymal tumors. National kidney cancer incidence rates, which include renal pelvis cancers, were used solely for population-level contextual comparison and not as histology-matched comparators to RCC. Results: Between 2015 and 2025, 205 RCC cases were identified statewide in WVU-affiliated hospital systems. Counties with documented or suspected PFOA exposure—defined by proximity to known PFAS-contaminated industrial sites, historical aqueous film-forming foam use, or contaminated groundwater or public water systems—demonstrated significantly elevated RCC prevalence. Statistically significant increases were observed in Berkeley (RR 2.80, 95% CI 1.95–4.03), Harrison (RR 2.94, 95% CI 1.83–4.72), Jefferson (RR 3.10, 95% CI 1.93–4.98), Morgan (RR 3.21, 95% CI 1.43–7.25), and Lewis (RR 5.29, 95% CI 2.71–10.33) counties. All associations were statistically significant (p < 0.05). These counties cluster in the Eastern Panhandle and north-central regions of West Virginia, regions with historical industrial activity, documented PFAS contamination, and downstream groundwater migration. No similar geographic clustering was observed for comparator cancers. Conclusions: WV counties with historical PFOA exposure demonstrate substantially increased RCC prevalence. This geographic specificity is biologically plausible, as PFAS undergo renal tubular reabsorption, leading to intrarenal accumulation and prolonged tissue residence, a pathway associated with chronic tubular injury and renal carcinogenesis. These findings support exposure-informed cancer surveillance and further analytic studies in environmentally impacted Appalachian communities.