JAK-STAT 通路相关基因与淋巴瘤风险的关联:一项欧洲病例对照研究(EpiLymph)的结果。

Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph).

机构信息

Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

出版信息

Br J Haematol. 2011 May;153(3):318-33. doi: 10.1111/j.1365-2141.2011.08632.x. Epub 2011 Mar 21.

Abstract

Previous studies have suggested an important role for the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in tumour development. Therefore, we explored genetic variants in JAK-STAT pathway associated genes with lymphoma risk. In samples of the EpiLymph case-control study we genotyped 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArray™ Technology (Illumina, San Diego, CA, USA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (B-NHL) and most frequent B-NHL subtypes. Among 210 relevant JAK-STAT pathway-related SNPs, polymorphisms in nine genes (BMF, IFNG, IL12A, SOCS1, STAT1, STAT3, STAT5A, STAT6, TP63) were significantly associated with lymphoma risk. At a study-wise significance level, we obtained a risk reduction of 28% among carriers of the heterozygous genotype of the STAT3 variant (rs1053023) for B-NHL. For six other variants within the STAT3 gene we observed an inverse association with different lymphoma subtypes. A reduced risk for HL was observed for the heterozygous genotype of the STAT6 SNP (rs324011). This is an explorative investigation to examine associations between JAK-STAT signalling related genes and lymphoma risk. The results implicate a relevant role of certain pathway-related genes in lymphomagenesis, but still need to be approved by independent studies.

摘要

先前的研究表明,Janus 激酶-信号转导和转录激活因子(JAK-STAT)信号通路在肿瘤发生中起着重要作用。因此,我们探索了与淋巴瘤风险相关的 JAK-STAT 通路相关基因中的遗传变异。在 EpiLymph 病例对照研究的样本中,我们使用 GoldenGate BeadArray™ 技术(Illumina,圣地亚哥,加利福尼亚州,美国)对 1536 个单核苷酸多态性(SNP)进行了基因分型。在这里,我们报告了 JAK-STAT 通路的选定 SNP 和单倍型与霍奇金淋巴瘤(HL)、B 细胞非霍奇金淋巴瘤(B-NHL)和最常见的 B-NHL 亚型风险之间的关联。在 210 个相关的 JAK-STAT 通路相关 SNP 中,9 个基因(BMF、IFNG、IL12A、SOCS1、STAT1、STAT3、STAT5A、STAT6、TP63)中的多态性与淋巴瘤风险显著相关。在研究层面上,我们发现 B-NHL 患者杂合基因型携带者的 STAT3 变异(rs1053023)的风险降低了 28%。我们还观察到 STAT3 基因内的六个其他变体与不同的淋巴瘤亚型呈反比关系。STAT6 SNP(rs324011)的杂合基因型与 HL 风险降低相关。这是一项探索性研究,旨在研究 JAK-STAT 信号相关基因与淋巴瘤风险之间的关联。结果表明,某些通路相关基因在淋巴瘤发生中起着重要作用,但仍需要通过独立研究加以证实。

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