Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph)
Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph)
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DOI：
10.1111/j.1365-2141.2011.08632.x
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发表时间：
2011-05-01
影响因子：
6.5
通讯作者：
Nieters, Alexandra
中科院分区：
文献类型：
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作者：
Butterbach, Katja;Beckmann, Lars;Nieters, Alexandra
先前的研究表明Janus激酶信号转导和转录激活因子（JAK-STAT）信号通路在肿瘤发展中起重要作用。因此，我们探索了与淋巴瘤风险相关的JAK-STAT通路相关基因的遗传变异。在癫痫病例对照研究的样本中，我们使用GoldenGate BeadArray （TM）技术（Illumina, San Diego， CA， USA）对1536个单核苷酸多态性（snp）进行了基因分型。在这里，我们报告了选定的snp和JAK-STAT通路的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亚型的风险之间的关联。在210个与JAK-STAT通路相关的snp中，9个基因（BMF、IFNG、IL12A、SOCS1、STAT1、STAT3、STAT5A、STAT6、TP63）的多态性与淋巴瘤风险显著相关。在研究显著性水平上，我们获得了STAT3变异（rs1053023）杂合基因型携带者患B-NHL的风险降低28%。对于STAT3基因内的其他六种变异，我们观察到它们与不同的淋巴瘤亚型呈负相关。STAT6 SNP （rs324011）的杂合基因型降低了患HL的风险。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系。这些结果暗示了某些通路相关基因在淋巴瘤发生中的相关作用，但仍需要独立研究的批准。
P>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 (TM) 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.