Matrix metalloproteinase (MMP)-1 and MMP-3 gene variations affect MMP-1 and -3 serum concentration and associates with breast cancer

Mol Biol Rep. 2020 Dec;47(12):9637-9644. doi: 10.1007/s11033-020-05962-x. Epub 2020 Nov 10.

Abstract

Matrix metallopeptidases (MMPs) 1 and 3 have been shown to contribute to the initiation, and progression of different cancers, including breast cancer (BC). In this study, we aimed to examine the relations between polymorphisms of MMP1 (rs1799750) and MMP3 (rs632478) and their circulating levels with BC. The polymorphisms were genotyped by PCR-based Restriction Fragment Length Polymorphism (RFLP) and Allele-Specific PCR (AS-PCR) among 100 patients and 100 controls. MMP1 and MMP3 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotype distributions of MMP1 and MMP3 genes showed significant difference between patients and controls. The distribution of 2G/2G, 1G/2G and 1G/1G genotypes for MMP1 was 74%, 2% and 24% in the patients and 38%, 2% and 60% in the controls, respectively (P = 0.0001). For MMP3 the distribution of C/C, A/C and A/A genotypes was 28%, 54% and 18% in patients and 48%, 40% and 12% in controls, respectively (P = 0.01). For MMP1, the 2G/2G genotype was linked with a higher risk of BC when compared with that of the 1G/1G genotype (OR = 4.86; 95% CI = 2.63-8.99; P = 0.0001). For MMP3, in co-dominant model, there was a higher risk of BC in A/A and A/C genotype carriers (A/A: OR = 2.57; 95% CI = 1.08-6.11; P = 0.03) (A/C: OR = 2.31 95% CI = 1.24-4.30; P = 0.008). We also showed that MMP1 and MMP3 serum level was significantly increased in BC patients compared to controls. MMP1 and MMP3 genetic variations and their circulating levels are both significantly related to BC.

Keywords: Breast cancer; MMP1; MMP3; Polymorphism; Serum.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / physiopathology
  • Alleles
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cigarette Smoking / physiopathology
  • Female
  • Gene Expression
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Matrix Metalloproteinase 1 / blood
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 3 / blood
  • Matrix Metalloproteinase 3 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Risk Factors
  • Surveys and Questionnaires

Substances

  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1