Prognostic relevance of genetic variants involved in immune checkpoints in patients with colorectal cancer

Purpose: Genetic polymorphisms in genes involved in the immune response are already known to affect the anti-tumor immune response. This study systematically investigated the association of 14 functional SNPs in a panel of 7 genes (CCL2, CCR2, NT5E, IDO1, LAG3, PDL1, and PDCD1) involved in immune response checkpoints with the survival outcomes of Korean patients with colorectal cancer (CRC). Methods: The genomic DNA from 668 patients with curatively resected CRC was analyzed using a Sequenom MassARRAY, along with the association with recurrence-free survival (RFS) and overall survival (OS). Results: Among the 14 SNPs, CCL2 rs4586 and PDCD1 rs10204525 were found to have an influence on the survival outcomes of the patients with resectable CRC. CCL2 rs4586 showed a significant correlation with OS in a recessive model in a univariate analysis, as well as a multivariate analysis. In addition, PDCD1 rs10204525 revealed a significant association with RFS and OS in a recessive model in a univariate analysis and exhibited a significant impact in a multivariate analysis. Conclusion: In conclusion, this results suggest that the genetic predisposition of the host may affect the anti-tumor immune reaction in CRC. The results of this study may also be helpful when selecting targets for novel drug development to promote the anti-tumor immune response.