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.
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.
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DOI：
10.1371/journal.pone.0090008
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang LY
中科院分区：
文献类型：
--
作者：
Fan QH;Yu R;Huang WX;Cui XX;Luo BH;Zhang LY
胃癌（包括贲门癌和非贲门癌）是世界范围内第二大常见的癌症相关死亡原因。通过全基因组关联研究（GWASs），亚洲人群中的非贲门部胃癌遗传易感性位点亚组已得到解决。本研究旨在探讨长基因间非编码RNA（lincRNA）单核苷酸多态性（SNPs）与中国人群非贲门部胃癌易感性的关系。我们选择了位于非贲门胃癌风险相关位点的长基因间非编码RNA（lincRNA），并确定了位于lincRNA外显子区域内的10个SNP。我们使用logistic回归分析在438例非贲门部胃癌患者和727例对照受试者中检测lincRNA外显子的遗传多态性是否与非贲门部胃癌风险相关。通过生物化学测定进一步检查功能相关性。我们发现lincRNA-NR_024015 rs 8506 AA携带者与非贲门胃癌的风险显著相关（与rs 8506 AG或GG基因型相比，校正比值比[OR]= 1.56，95%CI =1.03-2.39）。 进一步分层分析显示，吸烟者亚组的风险效应更明显（P = 0.001）。 生化分析表明，rs 8506 G>A处的G至A碱基改变破坏了has-miR-526 b的结合位点，从而影响lincRNA-NR_024015的转录活性并影响细胞增殖。我们的本研究建立了lincRNA-NR_024015外显子中的rs 8506 G>A多态性与非贲门胃癌风险之间的稳健关联。
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.
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