Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients

Kazuhiro Yamamoto, Kazuaki Shinomiya, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity. Aim: Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs). Patients and Methods: Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development. Results: The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80–10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 % CI, 2.38–48.07; P = 0.001). In a time-to-event Kaplan–Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009). Conclusions: The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.[MediaObject not available: see fulltext.]

Original languageEnglish
Pages (from-to)93-99
Number of pages7
JournalTargeted Oncology
Volume11
Issue number1
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

Renal Cell Carcinoma
Protein-Tyrosine Kinases
Single Nucleotide Polymorphism
Foot
Hand
Skin
Genotype
Odds Ratio
Confidence Intervals
STAT3 Transcription Factor
Linkage Disequilibrium
Keratinocytes
Alleles
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors : A Retrospective Analysis in Japanese Patients. / Yamamoto, Kazuhiro; Shinomiya, Kazuaki; Ioroi, Takeshi; Hirata, Sachi; Harada, Kenichi; Suno, Manabu; Nishioka, Tatsuya; Kume, Manabu; Makimoto, Hiroo; Nakagawa, Tsutomu; Hirano, Takeshi; Bito, Toshinori; Nishigori, Chikako; Miyake, Hideaki; Fujisawa, Masato; Hirai, Midori.

In: Targeted Oncology, Vol. 11, No. 1, 01.02.2016, p. 93-99.

Research output: Contribution to journalArticle

Yamamoto, K, Shinomiya, K, Ioroi, T, Hirata, S, Harada, K, Suno, M, Nishioka, T, Kume, M, Makimoto, H, Nakagawa, T, Hirano, T, Bito, T, Nishigori, C, Miyake, H, Fujisawa, M & Hirai, M 2016, 'Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients', Targeted Oncology, vol. 11, no. 1, pp. 93-99. https://doi.org/10.1007/s11523-015-0382-9
Yamamoto, Kazuhiro ; Shinomiya, Kazuaki ; Ioroi, Takeshi ; Hirata, Sachi ; Harada, Kenichi ; Suno, Manabu ; Nishioka, Tatsuya ; Kume, Manabu ; Makimoto, Hiroo ; Nakagawa, Tsutomu ; Hirano, Takeshi ; Bito, Toshinori ; Nishigori, Chikako ; Miyake, Hideaki ; Fujisawa, Masato ; Hirai, Midori. / Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors : A Retrospective Analysis in Japanese Patients. In: Targeted Oncology. 2016 ; Vol. 11, No. 1. pp. 93-99.
@article{7a0fe216202a4a4784c0e1f198971dea,
title = "Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients",
abstract = "Background: Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity. Aim: Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs). Patients and Methods: Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development. Results: The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 {\%} confidence interval [CI], 1.80–10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 {\%} CI, 2.38–48.07; P = 0.001). In a time-to-event Kaplan–Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009). Conclusions: The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.[MediaObject not available: see fulltext.]",
author = "Kazuhiro Yamamoto and Kazuaki Shinomiya and Takeshi Ioroi and Sachi Hirata and Kenichi Harada and Manabu Suno and Tatsuya Nishioka and Manabu Kume and Hiroo Makimoto and Tsutomu Nakagawa and Takeshi Hirano and Toshinori Bito and Chikako Nishigori and Hideaki Miyake and Masato Fujisawa and Midori Hirai",
year = "2016",
month = "2",
day = "1",
doi = "10.1007/s11523-015-0382-9",
language = "English",
volume = "11",
pages = "93--99",
journal = "Targeted Oncology",
issn = "1776-2596",
publisher = "Springer Paris",
number = "1",

}

TY - JOUR

T1 - Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors

T2 - A Retrospective Analysis in Japanese Patients

AU - Yamamoto, Kazuhiro

AU - Shinomiya, Kazuaki

AU - Ioroi, Takeshi

AU - Hirata, Sachi

AU - Harada, Kenichi

AU - Suno, Manabu

AU - Nishioka, Tatsuya

AU - Kume, Manabu

AU - Makimoto, Hiroo

AU - Nakagawa, Tsutomu

AU - Hirano, Takeshi

AU - Bito, Toshinori

AU - Nishigori, Chikako

AU - Miyake, Hideaki

AU - Fujisawa, Masato

AU - Hirai, Midori

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity. Aim: Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs). Patients and Methods: Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development. Results: The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80–10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 % CI, 2.38–48.07; P = 0.001). In a time-to-event Kaplan–Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009). Conclusions: The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.[MediaObject not available: see fulltext.]

AB - Background: Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity. Aim: Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs). Patients and Methods: Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development. Results: The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80–10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 % CI, 2.38–48.07; P = 0.001). In a time-to-event Kaplan–Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009). Conclusions: The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.[MediaObject not available: see fulltext.]

UR - http://www.scopus.com/inward/record.url?scp=84958749776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958749776&partnerID=8YFLogxK

U2 - 10.1007/s11523-015-0382-9

DO - 10.1007/s11523-015-0382-9

M3 - Article

C2 - 26300443

AN - SCOPUS:84958749776

VL - 11

SP - 93

EP - 99

JO - Targeted Oncology

JF - Targeted Oncology

SN - 1776-2596

IS - 1

ER -