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Matrix metalloproteinase polymorphisms and bladder cancer risk

A Karim Kader1, Lina Shao, Colin P Dinney

  • 1Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Cancer Research
|December 21, 2006
PubMed

Insights

Genetic variations in matrix metalloproteinases (MMP) are linked to bladder cancer risk. Specific MMP-9 and MMP-12 polymorphisms showed associations with invasive bladder cancer, especially in light smokers.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Matrix metalloproteinases (MMPs) play a role in the tumor microenvironment and are implicated in bladder cancer development.
  • Previous research has not explored the association between specific MMP gene polymorphisms and bladder cancer risk.

Purpose of the Study:

  • To investigate the association between single nucleotide polymorphisms (SNPs) and microsatellite polymorphisms in MMP genes and bladder cancer risk.
  • To analyze individual, combined, haplotype, and diplotype associations of MMP polymorphisms with bladder cancer risk.

Main Methods:

  • Genotyping of 11 SNPs and one microsatellite polymorphism in MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12.
  • Case-control study involving 560 Caucasian bladder cancer patients and 560 matched controls.
  • Statistical analyses including individual, combination, haplotype, diplotype, and smoke-stratified analyses.

Main Results:

  • No significant association was found between individual MMP polymorphisms and overall bladder cancer risk.
  • The MMP-9 microsatellite allele (>=24 CA repeats) and MMP-12-82 GG polymorphism were associated with increased risk of invasive bladder cancer.
  • Smoke-stratified analyses revealed associations between MMP polymorphisms and bladder cancer risk, particularly in light smokers. Linkage disequilibrium was observed among several MMP SNPs.

Conclusions:

  • Genetic variations within the MMP gene family are associated with bladder cancer risk.
  • Heavy carcinogen exposure may diminish the genetic influence of MMP polymorphisms.
  • A multigenic, pathway-based approach is crucial for accurate bladder cancer risk assessment.

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