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

Gene. 2015 Apr 25;561(1):88-94. doi: 10.1016/j.gene.2015.02.014. Epub 2015 Feb 11.


Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Colorectal cancer; Haplotype; IL-17A; IL-17F; IL-23R; Single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-17 / blood
  • Interleukin-17 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Interleukin / genetics*
  • Sequence Analysis, DNA


  • IL17A protein, human
  • IL17F protein, human
  • IL23R protein, human
  • Interleukin-17
  • Receptors, Interleukin