Associations of ICOS and PD.1 Gene Variants with Colon Cancer Risk in The Iranian Population

Background: Positive and negative co-stimulatory molecules are important factors determining the outcome of immune responses to the presence of tumors. Since co-stimulatory molecule expression may be affected by gene polymorphisms, we aimed to investigate associations between variants of PD.1 and ICOS and susceptibility to colon cancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (-538G/A) gene polymorphisms were evaluated by the PCR-RFLP method in 76 colon cancer patients and 73 healthy controls. Results: The frequencies of the GG genotype and the G allele at position -693 of the ICOS gene were significantly higher in the patient group (P=0.014 and p=0.0002), while the AA genotype was significantly more common in controls (P=0.0016). At position -538 of PD.1, GG genotype and G allele frequencies were higher in the patient group (P<0.0001and P<0.0001). Again, AA and also AG genotypes significantly predominated in controls (P<0.0001 and P=0.012). Regarding genotypes and alleles of ICOS at position +1720. Frequencies of GCG and GTG haplotypes were higher in patients compared to those of controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG haplotypes were higher in controls (P=0.0017, P<0.0001 and P=0.015). GTG/GTG and GTG/GCG double haplotypes were more frequent in patients compared to controls (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A) and ICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors for the development of colon cancer among Iranian patients.