Association of single-nucleotide polymorphisms in BCL2L1 and TACC3 with response to bacillus Calmette-Guérin intravesical therapy in non-muscle-invasive bladder cancer.

Abstract

260Background: Bacillus Calmette-Guérin intravesical therapy (BCG) has an important role in the management of high risk non-muscle-invasive bladder cancer (NMIBC). This study examines the association between germline single nucleotide polymorphisms (SNPs) and response to BCG therapy.Methods: Saliva or blood was collected from pts with NMIBC treated at a single center and diagnosed between 1984 and 2010. SNPs were selected based on reported associations with bladder cancer and BCG response, and genotyped using the Sequenom MassARRAY iPLEX system. No response to BCG was defined as the presence at 6 months of pathologically documented tumor in the bladder. Univariate logistic regression was used to test the association between the outcome of interest (no response to BCG at 6 months) and clinical variables (stage, grade and multifocality), or individual SNPs.Results: The cohort consisted of 158 pts with a median age of 65 years who received intravesical BCG for NMIBC (35.2% stage T1, 32.7% stage Ta and 31.4% stage Tis) with 93% having high-grade disease. At 6 months follow up, 22 (13.9%) patients showed no response to BCG. We successfully genotyped 80 of the 88 selected SNPs. Of these, 2 SNPs were associated with lack of response to BCG; rs798766 is an intronic SNP in TACC3 (OR for no response is 2.4 for each T allele relative to CC genotype, P=0.01), and rs1994251 an intronic SNP in BCL2L1 (OR for no response is 3.2 for each C allele relative to AA, p= 0.0008). Both SNPs remained significantly associated with lack of response after adjusting for predictive clinical variables.Conclusions: Single nucleotide polymorphisms of BCL2L1 and TACC3 may be predictive of BCG refractory bladder cancer. Future validation studies on independent datasets are needed to determine the clinical utility of these findings.