title: STAT3 polymorphism predicts interferon-alfa response in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-alpha) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-alpha immunotherapy.
  
  
  METHODS
  We carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-alpha for MRCC.
  
  
  RESULTS
  After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha. Linkage disequilibrium mapping revealed that the SNP in the 5' region of STAT3, rs4796793, was the most significant predictor of IFN-alpha response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN- by STAT3 suppression in an RCC cell line supported the results of the present association study.
  
  
  CONCLUSIONS
  The present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-alpha therapy in patients with MRCC. An efficient response marker for IFN-alpha needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.forename: Eijiro
authors.initials: E
authors.lastname: Nakamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toma
authors.forename: Hayakazu
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Susumu
authors.initials: S
authors.lastname: Kagawa
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Kanayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nose
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinukawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Jinnai
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Seki
authors.forename: Masanobu
authors.initials: M
authors.lastname: Takamatsu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Masui
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016898:Interferon-alpha / Q000627:therapeutic use*; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human