The impact of single-nucleotide polymorphisms on intravesical recurrence after bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer in a genome-wide association study

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

研究成果: Contribution to journalArticle査読

抄録

Objective: 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). Materials and methods: 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. Results: 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. Conclusion: 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.

本文言語英語
ページ(範囲)733.e17-733.e24
ジャーナルUrologic Oncology: Seminars and Original Investigations
39
10
DOI
出版ステータス出版済み - 10 2021

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 泌尿器学

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