The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes in Breast Cancer in Taiwan

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Title:	The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes in Breast Cancer in Taiwan
Authors:	An-Kuo Chou;Chieh-Lun Hs;Chieh-Lun Hsiao;Tzu-Ching Sh;Tzu-Ching Shih;Hwei-Chung W;Hwei-Chung Wang;Chia-Wen Tsa;Chia-Wen Tsai;Wen-Shin Cha;Wen-Shin Chang;Liang-Chih L;Liang-Chih Liu;Tzong-Der Wa;Tzong-Der Way;Jing-Gung Ch;Jing-Gung Chung;包大?;Da-Tian Bau
Contributors:	生物資訊與醫學工程學系
Date:	2017-09
Issue Date:	2017-11-03 06:05:42 (UTC+0)
Abstract:	Background/Aim: Metalloproteinases (MMPs) are a family of multifunctional proteins reported to be overexpressed in several types of cancers. However, the contribution of MMP8 genotype to oral cancer has not been elucidated. In this study, we focused on the contribution of polymorphisms in the promoter region of MMP-8 (C-799T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to Taiwanese oral cancer. Materials and Methods: In this case-control study, MMP-8 genotype, was examined among 788 patients with oral cancer and 956 gender- and age-matched healthy controls regarding its potential to determine oral cancer risk. Results: The distributions of MMP-8 C-799T, Val436Ala and Lys460Thr genotypes were not different between the oral cancer and non-cancer control groups. We also analyzed the allelic frequency distributions and no significant difference was found. As for geneenvironment interaction analysis, there was an increased risk for smokers, alcohol drinkers or betel quid chewers with variant MMP-8 C-799T or Val436Ala genotypes. Conclusion: Our findings suggest that the polymorphisms at MMP-8 C- 799T or Val436Ala may not play a major role in mediating personal risk of oral cancer; however, the detailed mechanisms require further investigation. Oral cancer is the eighth most commonly diagnosed cancer worldwide and has the highest male incidence density in Taiwan (1-3). There is regional variation in trends of oral cancer around the world, depending on the etiology and the risk factors involved. According to the government annual report, oral cancer is the fourth cause of cancer-related death among males in Taiwan and has been reported to be closely associated with tobacco, alcohol and betel nut consumption habits (4-7). In the past years, genomic biomarkers for oral cancer in Taiwan have been revealed (8-14) and further cellular etiological investigations and the interactions among the genetic and lifestyle factors will contribute to personalized cancer early detection and therapy. Matrix metalloproteinases (MMPs), also known as matrixins, are a family of calcium-dependent zinc-containing endopeptidases that play a key role in extracellular matrix homeostasis controlling the degradation of the components of connective tissue matrices (15, 16). In carcinogenesis, MMPs and their inhibitors are also related to the regulation of oral cancer invasion and metastasis (17-20). The imbalance of these MMPs and their interactions with specific inhibitors, e.g. the tissue inhibitors of metalloproteinases (TIMPs), may contribute to the initiation and progression of cancer (16, 17, 21). MMP-8, originally known as neutrophil collagenase, is expressed in not only neutrophils but also epithelial cells, fibroblasts, macrophages and endothelial cells (22-24). In recent years, mounting evidence showed that MMP-8 was capable to conduct cancer- and metastasissuppressive activities. Firstly, knockout of MMP induced a dramatic increase in the incidence of carcinogen-induced 585 This article is freely accessible online.
Relation:	ANTICANCER RESEARCH
Appears in Collections:	[Department of Biomedical informatics ] Journal Article

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