Functional genetic variant of WW domain containing oxidoreductase gene associated with urothelial cell carcinoma clinicopathologic characteristics and long-term survival

Objectives: In Taiwan, urothelial cell carcinoma (UCC) is a common malignancy of urinary tract that is associated with genetic and environmental carcinogens. WW domain-containing oxidoreductase (WWOX) has been identified as a tumor suppressor gene that associated with several cancers development and progression. The study aimed to explore the impact of WWOX gene polymorphisms on the clinicopathological status and prognosis of patients with UCC. Materials and methods: A total of 1,293 participants, including 431 patients with UCC and 862 healthy controls, were recruited for this study. Five polymorphisms of the WWOX gene were examined by a real-time PCR assay. Results: We found that individuals carrying TT polymorphism at rs11545028 and at least 1 G allele at rs3764340 associated with more susceptible to UCC. At least 1 A allele at rs12918952 associated with more advance disease and high grade tumor. Patients with T allele at rs11545028 associated with worse relapse free survival in all patients and worse disease specific survival (DSS) in male. Patients with A allele at rs12918952 associated with worse DSS in all patients and worse relapse free survival, DSS and overall survival in male. Conclusions: This is the first reported correlation between WWOX polymorphisms and UCC risk and clinicopathologic feature. Genetic variants of WWOX contribute to the pathologic staging, grading, and prognosis. The findings regarding these biomarkers provided a potential prediction of UCC progression.