title: The has-miR-526b binding-site rs8506G>a polymorphism in the lincRNA-NR_024015 exon identified by GWASs predispose to non-cardia gastric cancer risk.
abstract: Gastric cancer including the cardia and non-cardia types is the second frequent cause of cancer-related deaths worldwide. A subset of non-cardia gastric cancer genetic susceptibility loci have been addressed among Asian through genome-wide association studies (GWASs). This study was to evaluate the effects of single nucleotide polymorphisms (SNPs) of long intergenic non-coding RNAs (lincRNAs) on non-cardia gastric cancer susceptibility in Chinese populations. We selected long intergenic noncoding RNAs (lincRNAs) located in non-cardia gastric cancer risk-related loci and identified 10 SNPs located within lincRNA exonic regions. We examined whether genetic polymorphisms in lincRNAs exons are associated with non-cardia gastric cancer risk in 438 non-cardia gastric cancer patients and 727 control subjects in Chinese populations using logistic regression. Functional relevance was further examined by biochemical assays. We found that lincRNA-NR_024015 rs8506AA carrier was significantly associated with risk of non-cardia gastric cancer (adjusted odds ratio [OR] = 1.56, 95%CI = 1.03-2.39, compared with the rs8506 AG or GG genotype. Further stratification analysis showed that the risk effect was more pronounced in subgroups of smokers (P = 0.001). Biochemical analysis demonstrated that the G to A base change at rs8506G>A disrupts the binding site for has-miR-526b, thereby influencing the transcriptional activity of lincRNA-NR_024015 and affecting cell proliferation. Our present study established a robust association between the rs8506G>A polymorphism in the lincRNA-NR_024015 exon and the risk of non-cardia gastric cancer.
authors.affiliation: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Fan
authors.affiliation: Department of Oncology, Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal surgery, Wu Jiang first people's hospital, Suzhou, China.
authors.forename: Wei-Xian
authors.initials: WX
authors.lastname: Huang
authors.affiliation: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Cui
authors.affiliation: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Bing-Hui
authors.initials: BH
authors.lastname: Luo
authors.affiliation: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002299:Cardia / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003198:Computer Simulation; D005091:Exons / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C000595033:MIRN526 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C000603254:TDRG1 long non-coding RNA, human