title: The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070.
abstract: Metallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients and frequency-matched 1600 unaffected controls, we found that MMP13 rs2252070 G > A genetic polymorphism is significantly associated with ESCC risk in Chinese Han populations (GA: OR = 0.63, 95% CI = 0.54-0.74, P = 1.7 × 10(-6), AA: OR = 0.73, 95% CI = 0.66-0.81, P = 1.8 × 10(-6)). Interestingly, the rs2252070 G-to-A change was shown to diminish a Sp1-binding site in ESCC cells. Reporter gene assays indicated that the rs2252070 A allele locating in a potential MMP13 promoter has low promoter activities. After measuring MMP13 gene expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2252070 A protective allele carriers showed decreased oncogene MMP13 expression. Results of these analyses underline the support of the notion that MMP13 might function as a key oncogene in esophageal carcinogenesis.
authors.affiliation: Shandong Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.|Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China.
authors.forename: Huaixin
authors.initials: H
authors.lastname: Xing
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Pan
authors.affiliation: Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Sichong
authors.initials: S
authors.lastname: Han
authors.affiliation: Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Shang
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Shandong Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13