The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

Hettiaratchi, A., Hawkins, N. J., McKenzie, G., Ward, R. L., Hunt, J. E., Wakefield, D. and Di Girolamo, N. (2007) The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer. British Journal of Cancer, 96 5: 783-792. doi:10.1038/sj.bjc.6603630


Author Hettiaratchi, A.
Hawkins, N. J.
McKenzie, G.
Ward, R. L.
Hunt, J. E.
Wakefield, D.
Di Girolamo, N.
Title The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2007-03-12
Sub-type Article (original research)
DOI 10.1038/sj.bjc.6603630
Open Access Status DOI
Volume 96
Issue 5
Start page 783
End page 792
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Matrix metalloproteinase (MMP) overexpression has been implicated in the pathogenesis of colorectal carcinoma (CRC). Accumulating evidence suggests that MMP promoter single nucleotide polymorphisms (SNPs) effecting gene transcription are associated with enhanced susceptibility for the development of malignant disease, increased tumour invasiveness and poor patient survival. The aim of the current investigation was to determine whether such associations exist in a large CRC patient/control study population. Using an allelic discrimination real-time polymerase chain reaction, polymorphisms in the MMP-1, MMP-2 and MMP-3 gene promoters (-1607, -1306, and -1612 bp, respectively) were assessed in normal blood mononuclear cells from patients with CRC (n=503) and control subjects (n=471). Genotypes corresponding to each MMP SNP were correlated with tumour characteristics and clinical outcome. The frequency of each genotype was not statistically different between patients and control subjects and no significant differences were noted between the genotypes and tumour characteristics for the three MMP SNPs. CRC patients with the 2G/2G genotype for the MMP-1 SNP had significantly better 5-year survival compared to patients with a 1G allele (P<0.05). Our results demonstrate that CRC patients with a 2G/2G genotype in the MMP-1 gene promoter SNP have a favourable prognosis. Although our results were unexpected, given that this genotype is associated with enhanced MMP-1 transcriptional activity, they are consistent with recent data highlighting the anti-tumorigenic properties of MMPs.
Keyword Metalloproteinase
Real-time polymerase chain reaction
Single nucleotide polymorphism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Office of the Vice-Chancellor
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 46 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 46 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 11 Feb 2015, 20:59:35 EST by Ms Kate Rowe on behalf of School of Medicine