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 the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG
therapy for
NMIBC. 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 another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs161448, rs2764326, rs2814707, rs3787194, rs58081719, rs3095966, rs73520681, rs16877113, rs16887173, rs10269584, rs11772249, rs118137814, and rs61094339) associated with BCG failure. Following the cumulative analysis of candidate SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG
therapy. This study showed that several SNPs were possibly associated with outcome after intravesical BCG
therapy in a Japanese population with
NMIBC. The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies.