NOS3 895G>T and CBR3 730G>A Are Associated with Recurrence Risk in Non-Muscle-Invasive Bladder Cancer with Intravesical Instillations of THP.

OBJECTIVES: To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4'-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients.

METHODS: Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients.

RESULTS: The associations of patients' genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2-83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895G>T (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30-14.39, GT+TT vs. GG) and CBR3 730G>A (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07-6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients.

CONCLUSIONS: Our results suggest that NOS3 895G>T and CBR3 730G>A are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.