Fan Qiu-Hong, Yu Rong, Huang Wei-Xian, Cui Xi-Xi, Luo Bing-Hui, Zhang Li-Yuan
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Oncology, Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
PLoS One. 2014 Mar 4;9(3):e90008. doi: 10.1371/journal.pone.0090008. eCollection 2014.
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.
包括贲门癌和非贲门癌类型在内的胃癌是全球癌症相关死亡的第二大常见原因。通过全基因组关联研究（GWAS），亚洲人群中已经确定了一部分非贲门胃癌的遗传易感性位点。本研究旨在评估长链基因间非编码RNA（lincRNA）的单核苷酸多态性（SNP）对中国人群非贲门胃癌易感性的影响。我们选择了位于非贲门胃癌风险相关位点的长链基因间非编码RNA（lincRNA），并鉴定出位于lincRNA外显子区域内的10个SNP。我们使用逻辑回归分析了438例非贲门胃癌患者和727例中国人群对照受试者中lincRNA外显子的基因多态性是否与非贲门胃癌风险相关。通过生化分析进一步研究了功能相关性。我们发现lincRNA-NR_024015 rs8506AA携带者与非贲门胃癌风险显著相关（调整后的优势比[OR]=1.56，95%可信区间=1.03-2.39，与rs8506 AG或GG基因型相比）。进一步的分层分析表明，在吸烟者亚组中风险效应更为明显（P=0.001）。生化分析表明，rs8506G>A处的G到A碱基变化破坏了has-miR-526b的结合位点，从而影响lincRNA-NR_024015的转录活性并影响细胞增殖。我们目前的研究在lincRNA-NR_024015外显子中的rs8506G>A多态性与非贲门胃癌风险之间建立了强有力的关联。
