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3'UTR-HLA-G 多态性和循环 sHLA-G 与乳腺癌相关:来自荟萃分析的证据。

3'UTR-HLA-G polymorphisms and circulating sHLA-G are associated with breast cancer: Evidence from a meta-analysis.

机构信息

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia.

King Saud University, College of Science, Department of Zoology, Riyadh, Saudi Arabia.

出版信息

Immunol Lett. 2022 Aug;248:78-89. doi: 10.1016/j.imlet.2022.06.010. Epub 2022 Jun 22.

DOI:10.1016/j.imlet.2022.06.010
PMID:35752280
Abstract

BACKGROUND

Human leukocyte antigen-G (HLA-G) gene polymorphisms and circulating sHLA-G have often been linked to the risk of breast cancer (BC). However, the results remain controversial. To resolve this issue, we performed a meta-analysis of HLA-G gene polymorphisms and sHLA-G levels in BC.

METHODS

We performed a meta-analysis on the association of HLA-G 14-bp Insertion/Deletion (Ins/Del) and HLA-G +3142 C/G polymorphisms with BC as well as the relationship between sHLA-G and the disease outcome.

RESULTS

Pooled analysis showed a statistically significant association between the HLA-G 14-bp Ins/Del polymorphism and BC susceptibility for the overall population and for Caucasians. The Del allele and genotypes with at least one copy of the Del allele presented significant risks for BC. For HLA-G +3142 C/G polymorphism, the G allele significantly decreased the risk of BC for the overall population and for Caucasians, indicating that the G allele was a protective factor against BC and that the C allele was a significant risk factor for BC. The meta-analysis revealed a significantly increased level of sHLA-G patients with BC compared to the control group for the overall population, Caucasians and Asians.

CONCLUSION

The present meta-analysis showed a major association of both HLA-G 14-bp Ins/Del and +3142 C/G polymorphisms with BC susceptibility, suggesting Del and C variants as highly significant risk factors for BC. The present study also showed significantly higher sHLA-G levels in patients with BC compared to healthy controls. Our pooled results suggested a critical role of HLA-G in BC, thereby providing evidence to use HLA-G as a biomarker and a therapeutic tool.

摘要

背景

人类白细胞抗原-G(HLA-G)基因多态性和循环可溶性 HLA-G 经常与乳腺癌(BC)的风险相关。然而,结果仍存在争议。为了解决这个问题,我们对 HLA-G 基因多态性和 BC 中的可溶性 HLA-G 水平进行了荟萃分析。

方法

我们对 HLA-G 14 位核苷酸插入/缺失(Ins/Del)和 HLA-G+3142C/G 多态性与 BC 的相关性以及 sHLA-G 与疾病结局的关系进行了荟萃分析。

结果

汇总分析显示,HLA-G 14 位核苷酸 Ins/Del 多态性与整体人群和白种人群的 BC 易感性之间存在统计学显著关联。Del 等位基因和至少携带一个 Del 等位基因的基因型与 BC 显著相关。对于 HLA-G+3142C/G 多态性,G 等位基因显著降低了整体人群和白种人群患 BC 的风险,表明 G 等位基因是 BC 的保护因素,而 C 等位基因是 BC 的显著风险因素。荟萃分析显示,与对照组相比,BC 患者的 sHLA-G 水平显著升高,适用于整体人群、白种人和亚洲人。

结论

本荟萃分析显示,HLA-G 14 位核苷酸 Ins/Del 和+3142C/G 多态性与 BC 易感性有主要关联,表明 Del 和 C 变体是 BC 的高度显著风险因素。本研究还显示,与健康对照组相比,BC 患者的 sHLA-G 水平显著升高。我们的汇总结果表明 HLA-G 在 BC 中具有关键作用,从而为将 HLA-G 用作生物标志物和治疗工具提供了证据。

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