title: Interleukin-17FT7488 allele is associated with a decreased risk of colorectal cancer and tumor progression.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran. Electronic address: nematik1@gmail.com.
authors: Kazem
authors: K
authors: Nemati
authors: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran. Electronic address: golmoghadam@yahoo.com.
authors: Hossein
authors: H
authors: Golmoghaddam
authors: Institute for Colorectal Research Center, Faghihi Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: hoseiniv@sums.ac.ir.
authors: Seyed Vahid
authors: SV
authors: Hosseini
authors: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran; Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran. Electronic address: ghaderia@sums.ac.ir.
authors: Abbas
authors: A
authors: Ghaderi
authors: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran; Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran. Electronic address: mdoroud@sums.ac.ir.
authors: Mehrnoosh
authors: M
authors: Doroudchi
mesh_terms: D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C508717:IL17A protein, human; C440021:IL17F protein, human; C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin
keywords: Colorectal cancer; Haplotype; IL-17A; IL-17F; IL-23R; Single nucleotide polymorphisms