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.
authors.affiliation: Division of Pharmacokinetics, Kobe University Graduate School of Medicine.
authors.forename: Aimi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ioroi
authors.forename: Sachi
authors.initials: S
authors.lastname: Hirata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yano
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D044466:Asian People / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics*; D013280:Stomatitis / Q000139:chemically induced / Q000235:genetics*; D000077210:Sunitinib
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D007211:Indoles; D009363:Neoplasm Proteins; D011758:Pyrroles; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077210:Sunitinib