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

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). 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). 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. 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.