Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer

J Urol. 2009 May;181(5):2320-5. doi: 10.1016/j.juro.2009.01.012. Epub 2009 Mar 19.

Abstract

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer.

Materials and methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction using TaqMan(R) fluorescent probes.

Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042).

Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Chi-Square Distribution
  • Confidence Intervals
  • DNA, Neoplasm / analysis
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease / epidemiology*
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinases / genetics*
  • Middle Aged
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Probability
  • Prognosis
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / genetics*
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1