Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk

Cancer Genomics Proteomics. 2024 Sep-Oct;21(5):502-510. doi: 10.21873/cgp.20467.

Abstract

Background/aim: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk.

Materials and methods: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls.

Results: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05).

Conclusion: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.

Keywords: Breast cancer; genotype; matrix metalloproteinase-2; polymorphism; triple negative breast cancer.

MeSH terms

  • Adult
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Matrix Metalloproteinase 2* / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Risk Factors

Substances

  • Matrix Metalloproteinase 2
  • MMP2 protein, human