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

被引：17

作者：

Watanabe, Aimi ^{[1
]}

Yamamoto, Kazuhiro ^{[2
]}

Ioroi, Takeshi ^{[2
]}

Hirata, Sachi ^{[2
]}

Harada, Kenichi ^{[3
]}

Miyake, Hideaki ^{[3
]}

Fujisawa, Masato ^{[3
]}

Nakagawa, Tsutomu ^{[1
,2
]}

Yano, Ikuko ^{[1
,2
]}

Hiraiab, Midori ^{[1
,2
]}

机构：

[1] Kobe Univ, Grad Sch Med, Div Pharmacokinet, Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

[2] Kobe Univ Hosp, Dept Pharm, Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

[3] Kobe Univ, Grad Sch Med, Div Urol, Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2017年 / 40卷 / 04期

关键词：

sunitinib; polymorphism; stomatitis; adverse effect; renal cell carcinoma; P-GLYCOPROTEIN; GENE POLYMORPHISMS; SIGNAL TRANSDUCER; TYROSINE KINASE; EXPRESSION; ACTIVATION; SAFETY; PHARMACOKINETICS; TRANSPORTER; CREATININE;

D O I：

10.1248/bpb.b16-00875

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：458 / 464

页数：7

共 39 条

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