title: A common genetic variation in the promoter of miR-107 is associated with gastric adenocarcinoma susceptibility and survival.
abstract: BACKGROUND
  Global miRNA expression profile has been widely used to characterize human cancers. It is well established that genetic variants in miRNAs can modulate miRNA biogenesis and disease risk.
  
  
  METHODS
  Genome-wide miRNA microarray was employed for assessment of miRNA expression profile of gastric adenocarcinoma (GAC). The variants of significantly dysregulated miRNA were genotyped in test (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject sets.
  
  
  RESULTS
  MiRNA microarray revealed that 12 miRNAs including miR-107 significantly dysregulated in GAC tissues. The sequencing of the promoter of miR-107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele frequency (MAF)>5%. Analyzing their association with GAC risk and prognosis revealed that the C allele of rs2296616 (T>C) was significantly associated with the decreased risk of GAC among the test, validation and combined sets (TC/CC vs. TT, adjusted OR=0.39, 95% CI=0.31-0.49 for the combined set). However, the C allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted HR=1.49, 95% CI=1.01-2.20). In vivo evidence showed that the individuals with the rs2296616C allele had lower miR-107 expression compared with the homozygous T allele carriers.
  
  
  CONCLUSIONS
  miR-107 is dysregulated in GAC pathogenesis and the SNP rs2296616 may play a role in the process.
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China; Southeast University, School of Public Health, Ministry of Education, Key Laboratory of Environmental Medicine and Engineering, 87 Dingjiaqiao Street, Nanjing, China.
authors.forename: Shizhi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chunye
authors.initials: C
authors.lastname: Lv
authors.affiliation: Core Laboratory, Nantong Tumor Hospital, Nantong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Meiyun
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Core Laboratory, Nantong Tumor Hospital, Nantong, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Yixing Cancer Hospital, Yixing, China.
authors.forename: Weida
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huai-An, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Tao
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: drzdzhang@gmail.com.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: mwang@njmu.edu.cn.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality*
chemical_list: C549045:MIRN107 microRNA, human; D035683:MicroRNAs
keywords: Gastric cancer; Genetic susceptibility; Survival; miR-107; miRNA profile