A genetic polymorphism in CTLA-4 is associated with overall survival in sunitinib-treated patients with clear cell metastatic renal cell carcinoma.

Research paper by Xiaoyan X Liu, Jesse J JJ Swen, Meta H M MHM Diekstra, Epie E Boven, Daniel D Castellano, Hans H Gelderblom, Ron Hj RH Mathijssen, Sita H SH Vermeulen, Egbert E Oosterwijk, Kerstin K Junker, Max M Roessler, Kristin K Alexiusdottir, Asgerdur A Sverrisdottir, Marius T MT Radu, Valentin V Ambert, et al.

Indexed on: 02 Mar '18Published on: 02 Mar '18Published in: Clinical cancer research : an official journal of the American Association for Cancer Research


The survival of patients with clear cell metastatic renal cell carcinoma (cc-mRCC) has improved substantially since the introduction of tyrosine kinase inhibitors (TKIs). 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. 27 single nucleotide polymorphisms (SNPs) in(PD-L1)(PD-1) andwere 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. rs231775 andrs7866740 showed significant associations with OS in the discovery cohort after correction for age, gender and Heng prognostic risk group (HR=0.84, 95%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 of both SNPs with OS did not meet the significance threshold of p<0.05. After meta-analysis,rs231775 showed a significant association with OS (HR=0.83, 95%CI: 0.72-0.95, p=0.008). Patients with the GG-genotype had longer OS (35.1 months) compared to patients with an AG (30.3 months) or AA genotype (24.3 months). No significant associations with PFS were found. The G-allele of rs231775 in thegene is associated with improved OS in sunitinib-treated cc-mRCC patients and could potentially be used as a prognostic biomarker. Copyright ©2018, American Association for Cancer Research.

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