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.
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收藏
页码：458 / 464
页数：7
相关论文
共 39 条
[11]   Pharmacokinetics and Safety of Sunitinib Malate in Subjects With Impaired Renal Function [J].
Khosravan, Reza ;
Toh, Melvin ;
Garrett, May ;
La Fargue, JoAnn ;
Ni, Grace ;
Marbury, Thomas C. ;
Swan, Suzanne K. ;
Lunde, Norman M. ;
Bello, Carlo L. .
JOURNAL OF CLINICAL PHARMACOLOGY, 2010, 50 (04) :472-481
[12]   Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta [J].
Kobayashi, D ;
Ieiri, I ;
Hirota, T ;
Takane, H ;
Maegawa, S ;
Kigawa, J ;
Suzuki, H ;
Nanba, E ;
Oshimura, M ;
Terakawa, N ;
Otsubo, K ;
Mine, K ;
Sugiyama, Y .
DRUG METABOLISM AND DISPOSITION, 2005, 33 (01) :94-101
[13]   Sunitinib in Metastatic Renal Cell Carcinoma: Recommendations for Management of Noncardiovascular Toxicities [J].
Kollmannsberger, Christian ;
Bjarnason, Georg ;
Burnett, Patrick ;
Creel, Patricia ;
Davis, Mellar ;
Dawson, Nancy ;
Feldman, Darren ;
George, Suzanne ;
Hershman, Jerome ;
Lechner, Thomas ;
Potter, Amy ;
Raymond, Eric ;
Treister, Nathaniel ;
Wood, Laura ;
Wu, Shenhong ;
Bukowski, Ronald .
ONCOLOGIST, 2011, 16 (05) :543-553
[14]   Targeting STAT3 in Adoptively Transferred T Cells Promotes Their In Vivo Expansion and Antitumor Effects [J].
Kujawski, Maciej ;
Zhang, Chunyan ;
Herrmann, Andreas ;
Reckamp, Karen ;
Scuto, Anna ;
Jensen, Michael ;
Deng, Jiehui ;
Forman, Stephen ;
Figlin, Robert ;
Yu, Hua .
CANCER RESEARCH, 2010, 70 (23) :9599-9610
[15]   Sunitinib in metastatic renal cell carcinoma: An ethnic Asian subpopulation analysis for safety and efficacy [J].
Lee, Se-Hoon ;
Bang, Yung-Jue ;
Mainwaring, Paul ;
Ng, Christina ;
Chang, John W-C ;
Kwong, Philip ;
Li, Rubi K. ;
Sriuranpong, Virote ;
Toh, Chee-Keong ;
Yuan, Jinyu ;
Pitman Lowenthal, Susan ;
Chung, Hyun C. .
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 2014, 10 (03) :237-245
[16]   Expressions of ABCG2, CD133, and Podoplanin in Salivary Adenoid Cystic Carcinoma [J].
Li, Wuwei ;
Tamamura, Ryo ;
Wang, Bo ;
Liu, Qigui ;
Liu, Han ;
Liu, Tingjiao ;
Katase, Naoki ;
Xiao, Jing ;
Nagatsuka, Hitoshi .
BIOMED RESEARCH INTERNATIONAL, 2014, 2014
[17]   Association Study of a Functional Variant on ABCG2 Gene with Sunitinib-Induced Severe Adverse Drug Reaction [J].
Low, Siew-Kee ;
Fukunaga, Koya ;
Takahashi, Atsushi ;
Matsuda, Koichi ;
Hongo, Fumiya ;
Nakanishi, Hiroyuki ;
Kitamura, Hiroshi ;
Inoue, Takamitsu ;
Kato, Yoichiro ;
Tomita, Yoshihiko ;
Fukasawa, Satoshi ;
Tanaka, Tomoaki ;
Nishimura, Kazuo ;
Uemura, Hirotsugu ;
Hara, Isao ;
Fujisawa, Masato ;
Matsuyama, Hideyasu ;
Hashine, Katsuyoshi ;
Tatsugami, Katsunori ;
Enokida, Hideki ;
Kubo, Michiaki ;
Miki, Tsuneharu ;
Mushiroda, Taisei .
PLOS ONE, 2016, 11 (02)
[18]   Impact of Genetic Variation in Breast Cancer Resistance Protein (BCRP/ABCG2) on Sunitinib Pharmacokinetics [J].
Mizuno, Tomoyuki ;
Fukudo, Masahide ;
Terada, Tomohiro ;
Kamba, Tomomi ;
Nakamura, Eijiro ;
Ogawa, Osamu ;
Inui, Ken-ichi ;
Katsura, Toshiya .
DRUG METABOLISM AND PHARMACOKINETICS, 2012, 27 (06) :631-639
[19]   Pharmacokinetic Assessment of Efflux Transport in Sunitinib Distribution to the Brain [J].
Oberoi, Rajneet K. ;
Mittapalli, Rajendar K. ;
Elmquist, William F. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2013, 347 (03) :755-764
[20]   Serum creatinine level, a surrogate of muscle mass, predicts mortality in peritoneal dialysis patients [J].
Park, Jongha ;
Mehrotra, Rajnish ;
Rhee, Connie M. ;
Molnar, Miklos Z. ;
Lukowsky, Lilia R. ;
Patel, Sapna S. ;
Nissenson, Allen R. ;
Kopple, Joel D. ;
Kovesdy, Csaba P. ;
Kalantar-Zadeh, Kamyar .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2013, 28 (08) :2146-2155
1234