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长链非编码 RNA MEG3 rs3087918 与中国人群乳腺癌风险降低相关:一项病例对照研究。

LncRNA MEG3 rs3087918 was associated with a decreased breast cancer risk in a Chinese population: a case-control study.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

出版信息

BMC Cancer. 2020 Jul 15;20(1):659. doi: 10.1186/s12885-020-07145-0.

Abstract

BACKGROUND

LncRNA MEG3 expressed abnormally in various cancers including breast cancer, but no studies reported the correlation between MEG3 SNPs and breast cancer susceptibility among Chinese women.

METHODS

This study is aimed to explore the association between three SNPs of MEG3 (rs3087918, rs7158663, rs11160608) and breast cancer. The study is a population-based case-control study including 434 breast cancer patients and 700 healthy controls. Genotyping was performed using Sequenom MassArray technique. Function prediction of rs3087918 were based on RNAfold and lncRNASNP2 databases.

RESULTS

Pooled analysis indicated that rs3087918 was related to a decreased risk of breast cancer [GG vs. TT: OR (95%) = 0.67(0.45-0.99), P = 0.042; GG vs. TT + TG: OR (95%) = 0.69(0.48-0.99), P = 0.046], especially for women aged <=49 [GG vs. TT: OR (95%) = 0.40(0.22-0.73), P = 0.02]. Comparison between case groups showed genotype GG and TG/GG of rs3087918 were associated with her-2 receptor expression [GG vs. TT: OR (95%) = 2.37(1.24-4.63), P = 0.010; TG + GG vs. TT: OR (95%) = 1.50(1.01-2.24), P = 0.045]. We didn't find statistical significance for rs11160608, rs7158663 and breast cancer. Structure prediction based on RNAfold found rs3087918 may influence the secondary structure of MEG3. The results based on lncRNASNP2 indicated that rs3087918 may gain the targets of hsa-miR-1203 to MEG3, while loss the target of hsa-miR-139-3p and hsa-miR-5091 to MEG3.

CONCLUSIONS

MEG3 rs3087918 was associated with a decreased risk of breast cancer. MEG3 haplotype TCG may increase the risk of breast cancer.

摘要

背景

长链非编码 RNA MEG3 在包括乳腺癌在内的各种癌症中异常表达,但尚无研究报道 MEG3 SNP 与中国女性乳腺癌易感性之间的关系。

方法

本研究旨在探讨 MEG3 三个 SNP(rs3087918、rs7158663、rs11160608)与乳腺癌之间的关联。这是一项基于人群的病例对照研究,包括 434 名乳腺癌患者和 700 名健康对照。采用Sequenom MassArray 技术进行基因分型。基于 RNAfold 和 lncRNASNP2 数据库预测 rs3087918 的功能。

结果

汇总分析表明,rs3087918 与乳腺癌发病风险降低相关[GG 与 TT:OR(95%)=0.67(0.45-0.99),P=0.042;GG 与 TT+TG:OR(95%)=0.69(0.48-0.99),P=0.046],尤其是对于年龄<=49 岁的女性[GG 与 TT:OR(95%)=0.40(0.22-0.73),P=0.02]。病例组间比较显示,rs3087918 的 GG 基因型和 TG/GG 基因型与 her-2 受体表达相关[GG 与 TT:OR(95%)=2.37(1.24-4.63),P=0.010;TG+GG 与 TT:OR(95%)=1.50(1.01-2.24),P=0.045]。我们未发现 rs11160608、rs7158663 与乳腺癌之间存在统计学意义。基于 RNAfold 的结构预测发现,rs3087918 可能影响 MEG3 的二级结构。基于 lncRNASNP2 的结果表明,rs3087918 可能获得 MEG3 的 hsa-miR-1203 靶点,而失去 hsa-miR-139-3p 和 hsa-miR-5091 的靶点。

结论

MEG3 rs3087918 与乳腺癌发病风险降低相关。MEG3 单体型 TCG 可能增加乳腺癌发病风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d88/7362410/66ec1156faa5/12885_2020_7145_Fig1_HTML.jpg

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