Abstract
Kidney stone disease is a common and increasingly prevalent condition, with its incidence rising by 70% over the past two decades in the U.S. Lodgment of stones within the ureteral wall can cause urothelial injury, triggering inflammation, edema, and obstruction. Chronic inflammation has been linked to cancer development, contributing to tumorigenesis through cellular transformation, proliferation, invasion, angiogenesis, and metastasis. Studies suggest that recurrent nephrolithiasis can lead to a range of complications, including an increased risk of urinary tract cancer. This study investigates the association between kidney and ureteral stones and upper tract urothelial carcinoma (UTUC) risk using data from 502,144 individuals in the UK Biobank. We bidirectionally examined the presence of kidney stones and UTUC, applying a chi-square test to compute the odds ratio and assess statistical significance. A history of kidney stones was noted in 13,016 individuals, while 489,128 were stone-free. Among 511 UTUC cases, 50 had a history of kidney stones, whereas 461 were isolated UTUC. In contrast, 12,966 individuals had kidney stones without UTUC, and 488,667 were free of both conditions. Statistical analysis revealed an increased risk of UTUC in individuals with kidney stones [OR = 4.09 (95% CI 3.05-5.48), p < 0.001], indicating strong statistical significance. Our study demonstrates a fourfold increased risk of UTUC in individuals with a history of kidney stones. These findings highlight a significant association between kidney stones and UTUC, underscoring the need for further research on clinical management and cancer surveillance.