A Genetic Polymorphism in CTLA-4 Is Associated with Overall Survival in Sunitinib-Treated Patients with Clear Cell Metastatic Renal Cell Carcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Xiaoyan LiuHenk-Jan Guchelaar

Abstract

Purpose: The survival of patients with clear cell metastatic renal cell carcinoma (cc-mRCC) has improved substantially since the introduction of tyrosine kinase inhibitors (TKI). With the fact that TKIs interact with immune responses, we investigated whether polymorphisms of genes involved in immune checkpoints are related to the clinical outcome of cc-mRCC patients treated with sunitinib as first TKI.Experimental Design: Twenty-seven single-nucleotide polymorphisms (SNP) in CD274 (PD-L1), PDCD1 (PD-1), and CTLA-4 were tested for a possible association with progression-free survival (PFS) and overall survival (OS) in a discovery cohort of 550 sunitinib-treated cc-mRCC patients. SNPs with a significant association (P < 0.05) were tested in an independent validation cohort of 138 sunitinib-treated cc-mRCC patients. Finally, data of the discovery and validation cohort were pooled for meta-analysis.Results:CTLA-4 rs231775 and CD274 rs7866740 showed significant associations with OS in the discovery cohort after correction for age, gender, and Heng prognostic risk group [HR, 0.84; 95% confidence interval (CI), 0.72-0.98; P = 0.028, and HR, 0.73; 95% CI, 0.54-0.99; P = 0.047, respectively]. In the validation cohort, the associations o...Continue Reading

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