Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma.

ABSTRACT

UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.