title: STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population.
abstract: Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30-8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31-15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. yamakz@med.kobe-u.ac.jp.
authors.forename: Kazuhiro
authors.identifier: http://orcid.org/0000-0002-7513-6725
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ioroi
authors.affiliation: Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kanaya
authors.affiliation: Department of Clinical Psycho-Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shinomiya
authors.affiliation: Department of Clinical Psycho-Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Komoto
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Hirata
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Aimi
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Oncology Pharmaceutical Care and Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Suno
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishioka
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kume
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Makimoto
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.affiliation: Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Multitargeted tyrosine kinase inhibitors; Renal cell carcinoma; Signal transducer and activator of transcription 3; rs4796793 genotype
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