title: Evaluation of a novel functional single-nucleotide polymorphism (rs35010275 G>C) in MIR196A2 promoter region as a risk factor of gastric cancer in a Chinese population.
abstract: Single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been suggested to influence the occurrence and progression of cancer through altering the expression and biological function of miRNAs. The aim of this study was to investigate whether the potential functional SNPs in MIR196A2 promoter had effect on the susceptibility to gastric cancer (GC) in a Chinese population.We conducted a 2-stage case-control study (753 cases and 854 controls in testing set; 940 cases and 1061 controls in validation set) to evaluate the association between 2 potential functional SNPs in MIR196A2 promoter (rs12304647 A>C and rs35010275 G>C) and GC risk. The luciferase reporter assay and electrophoretic mobility shift assay were used to examine the functionality of the important polymorphism.We found that the rs35010275 C allele was significantly associated with the decreased risk of GC (adjusted odds ratio = 0.85, 95% confidence interval = 0.77-0.94) in the combined case-control studies. The miR-196a expression levels in GC tissues were significantly higher than that in corresponding adjacent normal tissues (P < 0.001). Besides, each allele of rs35010275 displayed completely opposite effects to influence the transcription activity of MIR196A2 promoter via recruiting different transcription factors or complexes.The functional rs35010275 G>C polymorphism in MIR196A2 promoter was significantly associated with miR-196a expression and influenced the genetic susceptibility to GC.
authors.affiliation: From the Department of Environmental Genomics (MX, YG, MK, MW, HZ, DW, ZZ), Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing; Department of Genetic Toxicology (MX, YG, MK, MW, DW, ZZ), The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Core Laboratory of Nantong Tumor Hospital (FQ, HZ), Nantong; Department of General Surgery (GT), Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huai-an; Department of General Surgery (WG), Yixing Cancer Hospital, Yixing; and Department of General Surgery (QZ), The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Fulin
authors.initials: F
authors.lastname: Qiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Meiyun
authors.initials: M
authors.lastname: Kang
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Guoquan
authors.initials: G
authors.lastname: Tao
authors.forename: Weida
authors.initials: W
authors.lastname: Gong
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: C542543:MIRN196 microRNA, human; D035683:MicroRNAs