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


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masatoshi
M
Eto
Tomomi
T
Kamba
Hideaki
H
Miyake
Masato
M
Fujisawa
Takao
T
Kamai
Hirotsugu
H
Uemura
Taiji
T
Tsukamoto
Haruhito
H
Azuma
Akio
A
Matsubara
Kazuo
K
Nishimura
Tsuyoshi
T
Nakamura
Osamu
O
Ogawa
Seiji
S
Naito
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
D016898:Interferon-alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human