Interleukin-17FT7488 allele is associated with a decreased risk of colorectal cancer and tumor progression

IL-17 family of cytokines and human IL-23R play important and sometimes contradictory roles in autoimmune and inflammatory diseases as well as human malignancies. Different alleles of this cytokine family may differentially affect IL-17 secretion. We sought to investigate the association of IL-17A, IL-17F and IL-23R gene polymorphisms with the susceptibility to colorectal cancer (CRC). The IL-17A rs2275913 (G197A), IL-17F rs763780 (T7488C), IL-23R rs11209026 and IL-23R rs1088967 SNPs were detected in 202 patients with colorectal cancer and 203 healthy age/sex matched controls by PCR-RFLP method. For evaluation of the functional relevance of these SNPs with IL-17A and IL-17F production, the serum levels of IL-17A and IL-17F were investigated in 107 and 109 patients as well as 33 and 52 healthy individuals, respectively, by ELISA assays. The IL-17F TT genotype [OR = 0.44, 95% CI: 0.21–0.94, P = 0.03] and T allele [OR = 0.46, 95% CI: 0.21–1.1, P = 0.03] were associated with a decreased risk of CRC compared with the TC genotype and C allele. Moreover, IL-17F TT genotype was significantly associated with well differentiation in tumors (P = 0.02). We also observed a significant association between the AG genotype of IL-17A G197A SNP with increased risk of colorectal cancer as compared to AA genotype (P = 0.001). The IL-17A concentrations in the sera of patients with CRC were significantly elevated compared to healthy individuals (P = 0.008), and serum level of IL-17A was significantly related to tumor size (P = 0.043). The A allele of IL-23R rs10889677 polymorphism was marginally associated with increased IL-17A levels in the sera of patients (P = 0.08). The genotype distributions of IL-23R rs11209026 and IL-23R rs10889677 SNPs were not significantly different between CRC patients and controls. The haplotypes of IL-17A G197A/IL-17F T7488C and IL-23R were not significantly associated with CRC. No IL-17F was detected in the sera of patients and only one healthy individual had IL-17F in his serum. Our findings suggest that the T allele of IL-17F T7488C polymorphism may be involved in reduced risk of CRC and IL-17A may be an attractive target for colorectal cancer immunotherapy.