Significant association between IL23R and IL17F polymorphisms and clinical features of colorectal cancer

Immunol Lett. 2014 Mar-Apr;158(1-2):189-94. doi: 10.1016/j.imlet.2014.01.002. Epub 2014 Jan 14.

Abstract

Th17cells are involved in inflammatory and autoimmune diseases. These cells may be involved in pathological processes mainly producing pro-inflammatory cytokines. Recently, it was shown that the IL23/IL17 pathway plays an important role in the development of inflammatory bowel disease. In general, genes encoding cytokines are genetically polymorphic and polymorphisms in genes IL23R el IL17F were shown associated with susceptibility to Crohn's disease and ulcerative colitis which in their turn are considered as risk factors for developing colorectal cancer (CRC). Our approach is to study IL17F and IL23R polymorphisms as risk factor associated with CRC in the Tunisian population in patients and healthy controls. Interesting, we noted a significant association between IL17F and IL23R polymorphisms and tumor location (p=0.0001 and p=0.049, respectively), tumor histology (p=0.007 and p=0.049, respectively) and tumor architecture (p=0.0000000001 and p=0.07, respectively) in CRC patients. We also showed a significant association of IL17F variant with an increased risk of TNM stage III/IV (p=0.007), showing an increased risk of advanced stage. Finally, we observed a positive link between IL17F polymorphism and CRC patients with lymph nodes (p=0.0000000001) and metastasis (p=0.00000009). However, we found no evidence to support a significant association between IL17F and IL23R polymorphisms and colorectal cancer susceptibility. Our findings suggest that IL17F and IL23R polymorphisms were significantly associated with clinical features variables. The IL17F cytokine appear to be involved in the control of tumor growth and invasion of gastrointestinal tumors. IL17 and IL23 polymorphisms or those of their receptors as important determinants of susceptibility to colorectal cancer are still subject to questioning.

Keywords: Clinical features; Colorectal cancer; IL17/IL23R; Immunity; Polymorphism; Th17 cells.

MeSH terms

  • Aged
  • Carcinogenesis
  • Carcinoma / genetics
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-17 / genetics*
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Polymorphism, Genetic
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / metabolism
  • Tunisia

Substances

  • IL23R protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Receptors, Interleukin