Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer

World J Gastroenterol. 2006 Aug 21;12(31):5037-43. doi: 10.3748/wjg.v12.i31.5037.

Abstract

Aim: To investigate the association between common single nucleotide polymorphisms (SNPs) in inflammatory response-related genes such as interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNFalpha), peroxisome proliferators-activated receptor gamma (PPARgamma), intercellular adhesion molecule-1 (ICAM-1) and the risk of colorectal cancer (CRC) in a group of Greek patients.

Methods: The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 (-174G>C), IL-8 (-251T>A), TNFalpha (-308G>A), ICAM-1 (R241G and K469E), and PPARgamma (Pro12Ala) genes and the risk of CRC.

Results: The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC (OR = 1.77, 95% CI: 1.34-2.34; OR = 1.83, 95% CI: 1.23-2.72; and OR = 1.35, 95% CI: 1.03-1.77 respectively). The IL-8 and TNFalpha polymorphisms had no effect. Whereas the PPARgamma Pro12 genotype was associated with increased risk of disease (OR = 1.78, 95% CI: 1.25-2.49).

Conclusion: The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.

MeSH terms

  • Aged
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Genotype
  • Greece
  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • Male
  • Middle Aged
  • PPAR gamma / genetics
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-6
  • Interleukin-8
  • PPAR gamma
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1