Integrative Comparison of mRNA Expression Patterns in Breast Cancers from Caucasian and Asian Americans with Implications for Precision Medicine.
Integrative Comparison of mRNA Expression Patterns in Breast Cancers from Caucasian and Asian Americans with Implications for Precision Medicine.
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白种人和亚裔美国人乳腺癌 mRNA 表达模式的综合比较对精准医学的影响。
DOI：
10.1158/0008-5472.can-16-1959
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发表时间：
2017-01-15
期刊：
影响因子：
11.2
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Shi Y;Steppi A;Cao Y;Wang J;He MM;Li L;Zhang J
亚裔美国人（AS）乳腺癌（BRCA）的发病率和死亡率明显低于白人美国人（CA）。虽然这种种族差异已被记录在案，但解释这种差异的潜在致病因素尚不清楚。我们通过整合基因组学方法比较BRCA的AS和CA病例之间的mRNA表达来解决这个问题。来自癌症基因组图谱的RNA-seq数据显示，mRNA表达在基因和途径水平上存在显著差异。CA患者的易感性和严重程度增加可能是环境和遗传风险因素协同作用的结果，花生四烯酸代谢和PPAR信号通路与环境和遗传因素有关。一项分析还添加了来自基因型组织表达计划的eQTL数据和来自1000个基因组计划的单核苷酸多态性（SNP）数据，确定了与差异表达基因相关的几个SNP。总的来说，我们发现的相关性可能有助于对基因型差异进行更有针对性的研究，这可能有助于解释CA和AS人群中BRCA发病率和死亡率的差异，并为精准医学提供信息。
Asian Americans (AS) have significantly lower incidence and mortality rates of breast cancer (BRCA) than Caucasian Americans (CA). While this racial disparity has been documented the underlying pathogenetic factors explaining it are obscure. We addressed this issue by an integrative genomics approach to compare mRNA expression between AS and CA cases of BRCA. RNA-seq data from the Cancer Genome Atlas showed that mRNA expression revealed significant differences at gene and pathway levels. Increased susceptibility and severity in CA patients were likely the result of synergistic environmental and genetic risk factors, with arachidonic acid metabolism and PPAR signaling pathways implicated in linking environmental and genetic factors. An analysis that also added eQTL data from the Genotype-Tissue Expression Project and single nucleotide polymorphism (SNP) data from the 1000 Genomes Project identified several SNPs associated with differentially expressed genes. Overall, the associations we identified may enable a more focused study of genotypic differences that may help explain the disparity in BRCA incidence and mortality rates in CA and AS populations and inform precision medicine.