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Genetic factors associated with cancer racial disparity – an integrative study across twenty‐one cancer types

机译:与癌症种族差异相关的遗传因素 - 跨二十一癌症类型的一项综合研究

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It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have generated a very large number of candidate factors, although there is modest agreement among the results of the different studies. Here, we performed an integrative analysis using genomic data of 21 cancer types from TCGA, GTEx, and the 1000 Genomes Project to identify biological factors contributing to racial disparity in cancer. We also built a companion website with additional results for cancer researchers to freely mine. Our study identified genes, gene families, and pathways displaying similar differential expression patterns between different racial groups across multiple cancer types. Among them, XKR9 gene expression was found to be significantly associated with overall survival for all cancers combined as well as for several individual cancers. Our results point to the interesting hypothesis that XKR9 could be a novel drug target for cancer immunotherapy. Bayesian network modeling showed that XKR9 is linked to important cancer-related genes, including FOXM1, cyclin B1, and RB1CC1 (RB1 regulator). In addition, metabolic pathways, neural signaling pathways, and several cancer-related gene families were found to be significantly associated with cancer racial disparities for multiple cancer types. Single nucleotide polymorphisms (SNPs) discovered through integrating data from the TCGA, GTEx, and 1000 Genomes databases provide biologists the opportunity to test highly promising, targeted hypotheses to gain a deeper understanding of the genetic drivers of cancer racial disparity and cancer biology in general.? 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
机译:众所周知,不同的种族群对某些癌症具有显着不同的发病率和死亡率。有人提出,生物因素在这些癌症种族差异中发挥着重要作用。以前关于患有癌症种族差异的生物因素的研究产生了很多候选因素,尽管不同研究结果之间存在适度的协议。在这里,我们使用来自TCGA,GTEX和1000个基因组项目的21种癌症类型的基因组数据进行了一致性分析,以确定有助于癌症种族差异的生物因素。我们还建立了一个伴侣网站,并为癌症研究人员提供了额外的癌症网站。我们的研究确定了在多种癌症类型之间显示不同种族群之间的类似差异表达模式的基因,基因家族和途径。其中,发现XKR9基因表达与所有癌症合并的所有癌症以及几种个体癌症的整体存活明显相关。我们的结果指出,XKR9可能成为癌症免疫疗法的新药靶标的有趣假设。贝叶斯网络建模表明,XKR9与重要的癌症相关基因相关联,包括Foxm1,Cyclin B1和RB1CC1(RB1调节器)。此外,发现代谢途径,神经信号传导途径和几个癌症相关的基因家族与多种癌症类型的癌症种族差异显着相关。通过整合来自TCGA,GTEX和1000个基因组数据库的数据来发现的单核苷酸多态性(SNP)提供生物学家有机会测试高度有前途的,有针对性的假设,以获得对癌症种族差异和癌症生物学的遗传驱动因素的更深入了解。还是2020作者。由FEBS Press和John Wiley&Sons Ltd发布代表欧洲生化社会联合会。

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