Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis

Gene. 2013 Mar 15;517(1):65-71. doi: 10.1016/j.gene.2012.12.085. Epub 2013 Jan 9.

Abstract

Purpose: Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis.

Methods: We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association.

Results: There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR=1.14, 95%CI=1.03-1.26, P=0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models.

Conclusions: MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found that MMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.

Publication types

  • Meta-Analysis

MeSH terms

  • Case-Control Studies
  • Humans
  • Lung Neoplasms / etiology*
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 3 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Factors

Substances

  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP1 protein, human
  • Matrix Metalloproteinase 1