A Single Nucleotide Polymorphism in the Matrix Metalloproteinase‐1 Promoter in Endometrial Carcinomas

Abstract

Recent studies demonstrated that a single guanine insertion polymorphism in a matrix metalloprotease‐1 promoter created an Ets binding site and affected the elevation of the transcriptional level of matrix metalloproteinase‐1 (MMP‐1). Furthermore, in tumor cell lines derived from melanoma and breast cancer, the incidence of the 2G/2G genotype was significantly higher than that in the normal population. To evaluate the contribution of this polymorphism in endometrial carcinomas, we genotyped 100 endometrial carcinomas and then analyzed immunoexpression of MMP‐1 in these carcinomas. We found that endometrial carcinoma patients showed a significantly higher rate of 1G/2G or 2G/2G genotype than control individuals, and that tumors containing the 2G allele(a) expressed MMP‐1 protein more frequently than those with 1G/1G genotype. Therefore, the single nucleotide polymorphism at the MMP‐1 promoter affected the expression level of the MMP‐1 protein, which may result in the association with more aggressive character in endometrial carcinoma. Our result suggests that the presence of 2G polymorphism at the MMP‐1 promoter may be one of the risk factors for the development and/or progression of endometrial carcinoma.

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

“…Our results showed no obvious LOH between the gDNA compared to the tumour-derived DNA in 100% of the randomly selected samples (n ¼ 61; data not shown) and this was comparable to other studies in renal (Hirata et al, 2003) and endometrial (Nishioka et al, 2000) carcinomas.…”

“…The discovery of polymorphisms in MMP promoters that alter gene expression has revealed strong associations between these genetic variants and increased susceptibility to the development of malignancies and other diseases (Henney et al, 2000;Ye, 2000). The most extensively studied MMP SNP in relation to cancer is the À1607 bp insertion/deletion in the MMP-1 promoter (Rutter et al, 1998;Nishioka et al, 2000;Ghilardi et al, 2001;Zhu et al, 2001;Hinoda et al, 2002;Tower et al, 2002;Wyatt et al, 2002;Zinzindohoue et al, 2005;Elander et al, 2006). Similar studies have been conducted for the MMP-2 (Miao et al, 2003) and MMP-3 (Ghilardi et al, 2002;Hinoda et al, 2002) gene promoter polymorphism in relation to disease susceptibility and metastatic behaviour.…”

“…A promoter containing this SNP (giving rise to the 2G genotype) displays significantly 'higher' transcriptional activity in normal and malignant cells compared to cells possessing a 1G allele (Rutter et al, 1998;Wyatt et al, 2002) with 'lower' transcriptional activity. 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).…”

Association of a single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter with glioblastoma

“…26 The presence of the additional guanine nucleotide at position 21607 in the MMP-1 promoter was discovered in a highly invasive melanoma cell line and since has been studied in several types of cancer. Cancers that have been examined for the MMP-1 promoter genotype include melanoma, 23 lung, 20 renal cell carcinoma, 21 cervical carcinoma, 27 oral squamous carcinoma, 28 breast, 24,29 ovarian, 18,25 endometrial carcinoma 30 and colorectal carcinoma. 19 In all but 2 studies (breast cancer 29 and melanoma), there was a significant difference in the distribution of the genotypes between the control population and the tumor population.…”

Epstein‐Barr virus latent membrane protein 1 induces the matrix metalloproteinase‐1 promoter via an Ets binding site formed by a single nucleotide polymorphism: Enhanced susceptibility to nasopharyngeal carcinoma

“…24 Previous studies reported a higher frequency of the 2G allele in patients with ovarian, endometrial, lung and colorectal cancers and malignant melanoma than in healthy controls, which suggests an association between cancer risk and MMP1 promoter polymorphism. [25][26][27][28][29][30] Recently, it has been reported that LMP1 induces MMP1 in transfected cell lines. The localized expression of MMP1 in NPC tissues has been also detected.…”