STAT3 polymorphism can predict the response to interferon-α therapy in patients with metastatic renal cell carcinoma.

Abstract

BACKGROUND:

In our 2007 retrospective study, we reported that single nucleotide polymorphisms (SNPs) in the signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) gene were significantly associated with better response to interferon (IFN)-α in patients with metastatic renal cell carcinoma (mRCC).

OBJECTIVE:

To prospectively confirm those results, the Japan Immunotherapy SNPs-Study Group for Kidney Cancer conducted this trial.

DESIGN, SETTING, AND PARTICIPANTS:

In this multicenter, prospective study, 203 eligible patients were enrolled. We evaluated the correlation between the antitumor effects of IFN-α and 11 SNPs (STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5) in eight genes in 180 patients who received IFN-α for >12 wk.

INTERVENTIONS:

Patients were treated with three doses per week of IFN-α 5 million IU.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

We analyzed the association of response to IFN-α and overall survival (OS) with genetic polymorphisms using a chi-square test and a logistic regression model.

RESULTS AND LIMITATIONS:

The response rate of IFN-α was 13.8% (28 of 203 patients; 9 complete responses [CRs], 19 partial responses [PRs]). The CR rate of 4.4% was higher than we expected. Response to IFN-α was not associated with any of the 11 SNPs examined. However, when we assessed patients with CR, PR, and stable disease >24 wk as a group representing those with clinical response, a significant association was observed between STAT3-2 (rs1905341) and the clinical response of IFN-α (p=0.039). Namely, C/C genotype of STAT3-2 was significantly associated with the clinical response of IFN-α and OS. These results were generated in Japanese patients and should be studied in other ethnic groups.

CONCLUSIONS:

This is the first prospective study demonstrating that a STAT3 polymorphism can be a predictive marker for treatment with IFN-α for patients with mRCC.

• Authors: Masatoshi Eto, Tomomi Kamba, Hideaki Miyake, Masato Fujisawa, Takao Kamai, Hirotsugu Uemura, Taiji Tsukamoto, Haruhito Azuma, Akio Matsubara, Kazuo Nishimura, Tsuyoshi Nakamura, Osamu Ogawa, Seiji Naito, Japan Immunotherapy SNPs-Study Group for Kidney Cancer
• Journal: European urology (Eur Urol) Vol. 63 Issue 4 Pg. 745-52 (Apr 2013) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 23063454 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Interferon-alpha
• STAT3 Transcription Factor
• STAT3 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Renal Cell (drug therapy, mortality)
• Drug Resistance, Neoplasm (genetics)
• Female
• Genotype
• Humans
• Interferon-alpha (therapeutic use)
• Japan
• Kidney Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prospective Studies
• STAT3 Transcription Factor (genetics)
• Survival Analysis
• Treatment Outcome