Linked Life Data

16353148

Source:http://linkedlifedata.com/resource/pubmed/id/16353148

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-3-6
pubmed:abstractText
Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. A single guanine insertion polymorphism (2G) in the MMP1 promoter sequence at -1,607 creates an Ets binding site and thus results in enhancing transcriptional activity. This study aimed to evaluate the contribution of this 2G polymorphism on susceptibility and aggressiveness of HNSCC. A panel of HNSCC cell lines and peritumoral fibroblasts were examined for the MMP1 genotypes and expression levels. Genomic DNA was extracted from peripheral blood of 300 patients with newly diagnosed HNSCC and from 300 age- and gender-matched cancer-free controls. Genotyping was carried out using a PCR-RFLP assay. The levels of MMP1 mRNA expression were evaluated by the quantitative RT-PCR and a correlation with different genotype was determined. Odds ratio (OR) for cancer risk were calculated using multivariate logistic regression. In addition, a correlation between the 2G/2G genotype and clinicopathological parameters was examined. Eleven out of 18 HNSCC cell lines showed the 2G/2G genotype (61%) and only 1 cell line had the 1G/1G genotype (5.6%). Cell lines with the 2G/2G genotype expressed significantly higher mean MMP1 mRNA level than those with other genotypes. In clinical model, subjects carrying the homozygous 2G/2G genotype had a higher risk of head and neck cancer compared with subjects with other genotypes (adjusted OR: 2.28; 95% CI: 1.58-3.27), controlling for major confounders. A correlation between promoter polymorphisms and the levels of MMP1 expression in cancer tissues was found, and this 2G/2G genotype was correlated with the adverse clinicopathological parameters. Finally, the highest level of MMP1 enhancement was demonstrated in the coculture of tumor cells and peritumoral fibroblasts of 2G homozygotes. These findings suggest that the presence of 2G polymorphism at the MMP1 promoter is associated with the development and progression of HNSCC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2548-53
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A functional polymorphism in the matrix metalloproteinase-1 gene promoter is associated with susceptibility and aggressiveness of head and neck cancer.
pubmed:affiliation
Department of Head and Neck Surgery, Siriraj Hospital Medical School, Mahidol University, Bangkok, Thailand. sipoc@mahidol.ac.th
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't