Genetic Analysis of a Single Nucleotide Polymorphism in the Matrix Metalloproteinase 1 Promoter in Breast Cancer
Abstract
Tumor invasion requires destruction of collagen, and is accomplished by matrix metalloproteinase-l (MMP-1). A single nucleotide polymorphism (SNP) in the MMP-1 promoter enhances transcription of this gene. The SNP is at - 1607 bp in the MMP-1 promoter, where an additional guanine (G) creates a binding site (5-AGGA-3 ) for the Ets transcription factors. Allele frequency is: 25% =1 G homozygous, 25% =2 G homozygous, and 50% = 1G/2G heterozygous. We hypothesized that the 2G SNP was associated with aggressive breast cancer. MMP-l is on chromosome 11q22.2-22.3, a region associated with Loss of Heterozygosity (LOH) in breast cancer, and that retaining the 2G allele after LOH provided tumors with an advantage for progression. Therefore, we (1) genotyped DNA from normal tissues and metastatic breast tumors for the SNP (2) evaluated tumors for LOH, and (3) measured MMP-1 mRNA levels. Of the 58 individuals genotyped, 24 were heterozygous, and of these only 5 underwent LOH, with 3 retaining the 2G allele and 2 retaining the 1G allele. mRNA analysis of tissues from 45 breast cancer patients revealed substantial MMP-l mRNA expression m 32. Thus, although LOH may not favor the 2G allele, MMP-l mRNA expression is common in breast cancer. MMP-1 may be a marker for women at risk for invasive/metastatic breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407580
Entities
People
- Constance E. Brinckerhoff
Organizations
- Dartmouth College