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三种致癌长非编码 RNA 基因中的 12 个多态性与肝癌风险和预后的关联:一项病例对照研究。

Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study.

机构信息

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China.

出版信息

World J Gastroenterol. 2018 Jun 21;24(23):2482-2490. doi: 10.3748/wjg.v24.i23.2482.

DOI:10.3748/wjg.v24.i23.2482
PMID:29930469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6010940/
Abstract

AIM

To evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes (, , ) with the risk and prognosis of hepatocellular cancer (HCC).

METHODS

Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs.

RESULTS

Three SNPs in , one promoter SNP in , and one haplotype of were associated with HCC risk. The rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models ( = 0.012, 0.017 and 0.049, respectively). rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models ( = 0.028). In addition, the two-way interaction of rs17501292- rs619586 polymorphisms showed a decreased effect on HCC risk ( = 0.028, OR = 0.30) and epistasis with each other. rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup ( = 0.049, HR = 0.12), and rs591291 showed significantly better prognosis in female and HBV negative subgroups ( = 0.022, HR = 0.37; = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis.

CONCLUSION

Specific lncRNA ( and ) SNPs have potential to be biomarkers for HCC risk and prognosis.

摘要

目的

评估三个癌基因长非编码 RNA(lncRNA)基因(、和)中的 12 个标签单核苷酸多态性(tagSNP)与肝细胞癌(HCC)风险和预后的关联。

方法

采用 KASP 法对 1338 例样本(包括 521 例 HCC 患者和频率匹配的 817 例对照)中的 12 个 tagSNP 进行基因分型。这些样本来自于 2012 年至 2015 年中国医科大学第一附属医院的一个无关中国人群。进行表达数量性状基因座(eQTL)分析,以进一步探讨有前途的 SNP 的潜在功能。

结果

在、中发现三个 SNP,在中发现一个启动子 SNP,和的一个单倍型与 HCC 风险相关。rs17501292、rs2067087 和 rs17427960 SNP 在等位基因模型下增加了 1.55、1.20 和 1.18 倍的 HCC 风险(=0.012、0.017 和 0.049,分别)。rs4102217 SNP 在显性模型下增加了 1.32 倍的 HCC 风险(=0.028)。此外,rs17501292-rs619586 多态性的双向相互作用显示出对 HCC 风险的降低作用(=0.028,OR=0.30),并相互作用。rs3807598 变异基因型在 HBV 阴性亚组中表现出显著延长的生存时间(=0.049,HR=0.12),rs591291 在女性和 HBV 阴性亚组中表现出显著更好的预后(=0.022,HR=0.37;=0.042,HR=0.25,分别)。在该研究中,eQTL 分析未观察到显著影响。

结论

特定的 lncRNA(和)SNP 有可能成为 HCC 风险和预后的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/6010940/47795fd5df04/WJG-24-2482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/6010940/47795fd5df04/WJG-24-2482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/6010940/47795fd5df04/WJG-24-2482-g001.jpg

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