Gene-gene interactions in gastrointestinal cancer susceptibility.
Gene-gene interactions in gastrointestinal cancer susceptibility.
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DOI：
10.18632/oncotarget.11701
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发表时间：
2016-10-11
期刊：
影响因子：
--
通讯作者：
Kang SJ
中科院分区：
文献类型：
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作者：
Kim J;Yum S;Kang C;Kang SJ
癌症产生于多种遗传和环境因素之间复杂的、多层次的相互作用。遗传学研究已经确定了多个与肿瘤易感性相关的基因座。然而，关于种系多态性如何相互作用以及如何与肿瘤内的体细胞突变相互作用来介导癌症特征的获得，我们知之甚少。在这里，我们调查了最近的研究显示基因相互作用，也被称为上位酶，影响遗传易感性在结直肠癌，胃癌和食管癌。我们也编目上位类型和癌症的标志，相对于相互作用的基因。共有22对基因变异对表现出不同程度的统计上位性，包括协同作用、冗余作用、抑制作用和共抑制作用。5个主要参与碱基切除修复的基因在相互作用网络中形成线性拓扑结构，MUTYH-OGG1-XRCC1-PARP1-MMP2， mTOR细胞增殖通路中的3个基因形成另一个线性网络，PRKAG2-RPS6KB1-PIK3CA。在核苷酸切除修复、解毒、增殖、TP53、TGF-β等途径中也发现离散成对上位。我们提出三种生物相互作用模式是统计上位的分子机制的基础。直接结合、线性途径和收敛模式在胃肠道癌症易感性中可以表现出任何程度的统计学上位性，这可能也适用于其他复杂疾病。这篇综述强调了癌症标志和易感基因之间的联系。
Cancer arises from complex, multi-layer interactions between diverse genetic and environmental factors. Genetic studies have identified multiple loci associated with tumor susceptibility. However, little is known about how germline polymorphisms interact with one another and with somatic mutations within a tumor to mediate acquisition of cancer traits. Here, we survey recent studies showing gene-gene interactions, also known as epistases, affecting genetic susceptibility in colorectal, gastric and esophageal cancers. We also catalog epistasis types and cancer hallmarks with respect to the interacting genes. A total of 22 gene variation pairs displayed all levels of statistical epistasis, including synergistic, redundant, suppressive and co-suppressive interactions. Five genes primarily involved in base excision repair formed a linear topology in the interaction network, MUTYH-OGG1-XRCC1-PARP1-MMP2, and three genes in mTOR cell-proliferation pathway formed another linear network, PRKAG2-RPS6KB1-PIK3CA. Discrete pairwise epistasis was also found in nucleotide excision repair, detoxification, proliferation, TP53, TGF-β and other pathways. We propose that three modes of biological interaction underlie the molecular mechanisms for statistical epistasis. The direct binding, linear pathway and convergence modes can exhibit any level of statistical epistasis in susceptibility to gastrointestinal cancers, and this is likely true for other complex diseases as well. This review highlights the link between cancer hallmarks and susceptibility genes.