Association of Single Nucleotide Polymorphisms in <i>STAT3</i>, <i>ABCB1</i>, and <i>ABCG2</i> with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients

• Watanabe Aimi

  Division of Pharmacokinetics, Kobe University Graduate School of Medicine

• Yamamoto Kazuhiro

  Department of Pharmacy, Kobe University Hospital

• Ioroi Takeshi

  Department of Pharmacy, Kobe University Hospital

• Hirata Sachi

  Department of Pharmacy, Kobe University Hospital

• Harada Kenichi

  Division of Urology, Kobe University Graduate School of Medicine

• Miyake Hideaki

  Division of Urology, Kobe University Graduate School of Medicine

• Fujisawa Masato

  Division of Urology, Kobe University Graduate School of Medicine

• Nakagawa Tsutomu

  Division of Pharmacokinetics, Kobe University Graduate School of Medicine Department of Pharmacy, Kobe University Hospital

• Yano Ikuko

  Division of Pharmacokinetics, Kobe University Graduate School of Medicine Department of Pharmacy, Kobe University Hospital

• Hirai Midori

  Division of Pharmacokinetics, Kobe University Graduate School of Medicine Department of Pharmacy, Kobe University Hospital

Bibliographic Information

Other Title

• Association of Single Nucleotide Polymorphisms in STAT3, ABCB1, and ABCG2 with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib : A Retrospective Analysis in Japanese Patients

Abstract

Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development. Stomatitis occurred in 22 out of 52 patients. The TT+TC genotypes at STAT3 rs744166 had an odds ratio of 5.00 against CC genotype for the stomatitis development (95% confident interval, 0.97–25.8). In the Kaplan–Meier method for the cumulative incidence of stomatitis, a statistically significant difference was observed between the TT+TC and CC genotypes in STAT3 rs744166 (p=0.037). Both multiple logistic regression analysis and Cox proportional-hazards regression analysis show STAT3 rs744166 TT+TC genotypes and serum creatinine in each patient were significant independent factors for stomatitis development. In conclusion, STAT3 polymorphism may be a novel risk factor for sunitinib-induced stomatitis in patients with mRCC.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 40 (4), 458-464, 2017

  The Pharmaceutical Society of Japan

Keywords

• sunitinib
• polymorphism
• stomatitis
• adverse effect
• renal cell carcinoma

Details

• CRID: 1390001204633854208
• NII Article ID: 130005530145
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b16-00875
• ISSN: 13475215
• ISSN: 09186158
• HANDLE: 20.500.14094/90004523
• NDL BIB ID: 028082135
• PubMed: 28381801
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028082135
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/4/40_b16-00875/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017347180
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed