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Background/aim Since androgens affect urothelial bladder cancer (UBC), we examined whether 5α-reductases (5-AR) have genomic alterations in UBC and whether 5α-reductase inhibitors (5-ARI) affect UBC. Materials and methods The cBioPortal was used to analyze genomic alternations of 5-ARs in UBC cancer genomic datasets. Next, we used the Taiwan National Health Insurance Research database to conduct a population-based case-control study to investigate the effect of a 5-ARI, finasteride on UBC incidence. We also performed an XTT assay to examine the direct effect of finasteride on UBC cells. Results We found that 5-AR genomic alternations were observed in 29% of UBC patients and patients with alternations had shorter disease-free survival. Also, the use of finasteride with >180 cDDDs reduced the risk of UBC. Finasteride could directly inhibit UBC cell growth. Conclusion Based on our findings, we concluded that 5-AR could be explored as a therapeutic target for UBC with 5-ARIs.

The DNA non-homologous end-joining repair gene XRCC6 (Ku70) plays a key role in both the DNA double-strand break (DSB) repair and cell cycle arrest. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that a variant in the XRCC6 gene was associated with susceptibility to renal cell carcinoma (RCC).In a hospital-based case-control study of 92 patients with RCC and 580 cancer-free controls, the frequency matched by age and sex, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with RCC risk were investigated in a Taiwanese population. At the same time, 30 adjacent renal tissue samples were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription.Compared with the TT genotype, the TC genotype had a significantly increased risk of RCC [adjusted odds ratio=2.24, 95% confidence interval=1.25-4.08, p=0.0175]. The in vivo mRNA expression in renal tissues revealed a statistically significant lower XRCC6 mRNA expression in samples with TC/CC genotypes compared to those with the TT genotype (p=0.0039).These evidence suggests that the XRCC6 T-991C genotype together with its mRNA expression are involved in the etiology of RCC and may be a marker for susceptibility to RCC in the population of Taiwan.