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• W2329781817 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCProteases such as the matrix metalloproteinase (MMP) family of proteases have emerged as being important to cancer aetiology and progression. Differences in gene and protein expression have been reported to be associated with many cancers and increased MMP expression is frequently reported to be associated with poor prognostic features. Although no MMP SNPs have been identified to be associated with cancer in all genome-wide association studies published to date, this is not be surprising given the extremely poor coverage of these gene families (1-38% for individual genes), and the knowledge that virtually all study designs to date have been underpowered to detect the small effect sizes expected for common SNPs. We have embarked on a study to assess the relevance of MMP expression and their SNPs in predisposition and prognosis of endometrial cancer, a largely hormonally driven cancer. An extensive literature review revealed that 62/69 studies reported overexpression of MMPs to be associated with poor prognostic features (grade, stage or survival) of hormone-related cancers, including endometrial cancer. Analysis of endometrial tumour MMP gene expression data from 18 different publications was undertaken to identify differentially expressed MMPs (>2-fold) associated with tumour predisposition and/or prognosis, based preferably on raw expression data but otherwise on reported gene lists. Although coverage of the MMP gene family was incomplete for the different expression platforms, this exercise prioritized 14 MMPs for further study in relation to risk and/or prognosis of endometrial cancer. We then mined the stage 1 results for the genome-wide association study we are undertaking to identify novel genetic variants associated with endometrial cancer risk, which involves comparison of 1285 Australian and British endometrial cancer cases of endometrioid subtype reporting Caucasian ethnicity scanned with the Illumina 610K BeadChip, and existing genome-wide scan control data available from the Wellcome Trust Case Control Consortium. A SNP falling in a prioritized MMP with only 19% coverage was found to be significant at P=0.002 (trend test). This SNP has been selected for confirmation in replication sample sets from 9 studies for association with endometrial cancer predisposition, and will be analyzed with SNPs from other prioritized MMP genes for association with prognostic indicators such as grade.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2842." @default.
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• W2329781817 title "Abstract 2842: Gene expression and genetic variation of the matrix metalloproteinase family: evidence for association with endometrial cancer risk and prognosis" @default.
• W2329781817 doi "https://doi.org/10.1158/1538-7445.am10-2842" @default.
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