Bacillus Calmette-Guérin (BCG) instillation therapy is widely used to reduce intravesical recurrence in non-muscle invasive bladder cancer (NMIBC). In this study, we aimed to reveal the genetic variations associated with intravesical recurrence after BCG therapy for NMIBC in a genome-wide association study (GWAS).
This study included Japanese patients with NMIBC, in whom genomic DNA was obtained from whole blood samples. The association between genetic variation and treatment failure was analyzed by GWAS in 44 patients treated with BCG instillation as a discovery cohort. Candidate single-nucleotide polymorphisms (SNPs) were examined separately in 47 patients treated with BCG instillation and in 62 patients treated with chemotherapeutic agent instillation as validation studies.
Among the 44 patients in the discovery cohort, 14 cases experienced intravesical recurrent diseases. GWAS identified 12 candidate SNPs (rs9374832, rs35176001, rs363765, rs2127120, rs4277759, rs73664140, rs1607282, rs12141654, rs4541358, rs6986852, rs12373386, and rs17637903). In the validation study, a genetic risk stratification model using the number of risk alleles in rs363765 and rs6986852 discriminated the risk of intravesical recurrence after BCG therapy, but not after non-BCG therapy.
This study suggested that several SNPs were associated with intravesical recurrence after BCG therapy for NMIBC. A genetic risk model may be useful to predict intravesical recurrence after BCG therapy, warranting further research and development for clinical application.
Urologic oncology. 2021 Jun 29 [Epub ahead of print]
Shohei Nagakawa, Masaki Shiota, Naohiro Fujimoto, Yoshiaki Yamamoto, Leandro Blas, Shigehiro Tsukahara, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Takeshi Uchiumi, Hideyasu Matsuyama, Masatoshi Eto
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ., Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan., Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan., Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.