Genome-wide association study on genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer.

Abstract

e17000 Background: Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. Methods: This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in the distinct cohort. Results: The genome-wide association study indicated 19 candidate SNPs associated with BCG failure. Consistent results were obtained in six of these SNPs in the validation cohort. Following the combinational use of validated SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. Conclusions: This study showed that several SNPs were associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The combinational use of these SNPs may have value in clinical applications, although this should be confirmed in future studies.