A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer

Auris Nasus Larynx. 2008 Sep;35(3):381-9. doi: 10.1016/j.anl.2007.12.002. Epub 2008 Feb 13.

Abstract

Objective: Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC).

Methods: In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry.

Results: We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049).

Conclusion: These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.

MeSH terms

  • Aged
  • Alleles
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Disease-Free Survival
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-8 / genetics*
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Tongue / pathology
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / pathology

Substances

  • Interleukin-8
  • Matrix Metalloproteinase 1