Absence of a Correlation between the Presence of a Single Nucleotide Polymorphism in the Matrix Metalloproteinase 1 Promoter and Outcome in Patients of Chondrosarcoma

Abstract

Purpose: Increased levels of matrix metalloproteinase 1 (MMP-1) expression have been associated with poor outcome in chondrosarcoma. The existence of a single nucleotide polymorphism creating an Ets-binding site in the MMP-1 promoter may be one mechanism for elevated MMP-1 transcription. The aim of our study was to identify the prevalence of this single nucleotide polymorphism (SNP) in chondrosarcoma patients, to determine its correlation with disease outcome, and to discern whether it could serve as a prognostic marker in patients with chondrosarcoma.Experimental Design: Sixty-seven chondrosarcoma specimens were selected sequentially from an established tumor bank with a median duration of 47 months follow-up (range, 24 to 179 months). DNA was extracted, amplified with PCR, and sequenced to determine presence (GG) or absence of the Ets-binding site created by the SNP.Results: Eighteen (27%) samples were homozygous for the absence of the Ets site, 34 (51%) were heterozygous for the SNP, and 15 (22%) were homozygous for the SNP. The 5-year overall survival rate for patients was 78, 80, and 84%, respectively (P ‫؍‬ 0.5527). The disease-free survival rate was 16, 63, and 76%, respectively (P ‫؍‬ 0.0801). The 5-year disease-free survival rate for patients with the homozygous G/G genotype was 16%, compared with 71% for patients who were either homozygous or heterozygous for the GG allele (P ‫؍‬ 0.0444). Conclusions:Despite a statistical correlation between MMP-1 gene expression and outcome in chondrosarcoma, this study demonstrates an absence of a correlation between the presence of the SNP and prognosis in patients with chondrosarcoma.

Association between Polymorphisms in the Promoter Regions of Matrix Metalloproteinases (MMPs) and Risk of Cancer Metastasis: A Meta-Analysis

“…The study was judged to be of good quality if the total score was over 6, otherwise, of poor quality. The total score of most studies was over 6 except for four studies [28]–[29], [31], [33] (Table S2). The information of healthy controls was not provided in the four studies.…”

“…Different genotyping methods were used in these studies, including the classical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 21 of 33 studies [17]–[21], [23], [25]–[30], [39], [41]–[48], PCR-allele specific refractory mutation system analysis (ARMS) in 2 studies [7], [40], TaqMan assay in 4 studies [19], [22], [34], [37], PCR-sequencing in 6 studies [24], [31], [33], [35]–[36], [38], and PCR – fluorescent fragment analysis in 2 studies [28], [32].…”

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

“…Several studies have identified strong linkage between this polymorphism and several common malignancies, including colorectal (Ghilardi et al, 2001;Hinoda et al, 2002;Zinzindohoue et al, 2005;Elander et al, 2006), endometrial (Nishioka et al, 2000), lung (Zhu et al, 2001), and ovarian (Kanamori et al, 1999) cancers and melanoma (Rutter et al, 1998;Tower et al, 2002). Polymorphisms in the promoter of MMP-2 (Miao et al, 2003), MMP-3 (Ghilardi et al, 2002), and MMP-7 (Zhang et al, 2005) have also been associated with increased susceptibility to the development of cancer, and to poorer prognosis, but these associations have not been found in all studies (Lei et al, 2002;Wenham et al, 2003;Fong et al, 2004;Krippl et al, 2004;Zinzindohoue et al, 2005).…”

Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line

“…An approach decreasing the ability of invasion and metastasis may facilitate the development of effective adjuvant therapy. In the processing of chondrosarcoma invasion and metastasis, the degradation of extracellular matrix (ECM) and the components of the basement membrane caused by the concerted action of proteinases, such as matrix metalloproteinases (MMP), cathepsins, and plasminogen activator, is a critical step in tumor invasion and metastasis [3,[5][6][7][8] . Among these enzymes, MMP-2 and MMP-9 degrade most components of the ECM directly and deeply involved in cancer invasion and metastasis [7,9] .…”