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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Carcinoma, Renal Cell, Female, Humans, Immunotherapy, Interferon-alpha, Japan, Kidney Neoplasms, Linkage Disequilibrium, Male, Neoplasm Metastasis, Odds Ratio, Polymorphism, Genetic, Polymorphism, Single Nucleotide, STAT3 Transcription Factor, Treatment Outcome.
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Does sTAT3 polymorphism predict interferon-alfa response in patients with metastatic renal cell carcinoma? Context: 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. 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. 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.
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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. Final Decision: yes