Patel Trupti N, Roy Soumyadipta, Ravi Revathi
Department of Medical Biotechnology, VIT University, Vellore 632014, Tamil Nadu, India.
Ecancermedicalscience. 2017 Jan 17;11:714. doi: 10.3332/ecancer.2017.714. eCollection 2017.
Gastric cancer, a malignant and highly proliferative condition, has significantly affected a large population around the globe and is known to be caused by various factors including genetic, epigenetic, and environmental influences. Though the global trend of these cancers is declining, an increase in its frequency is still a threat because of changing lifestyles and dietary habits. However, genetic and epigenetic alterations related to gastric cancers also have an equivalent contribution towards carcinogenic development. DNA methylation is one of the major forms of epigenetic modification which plays a significant role in gastric carcinogenesis. Methylation leads to inactivation of some of the most important genes like DNA repair genes, cell cycle regulators, apoptotic genes, transcriptional regulators, and signalling pathway regulators; which subsequently cause uncontrolled proliferation of cells. Mutations in these genes can be used as suitable prognostic markers for early diagnosis of the disease, since late diagnosis of gastric cancers has a huge negative impact on overall patient survival. In this review, we focus on the important epigenetic mutations that contribute to the development of gastric cancer and the molecular pathogenesis underlying each of them. Methylation, acetylation, and histone modifications play an integral role in the onset of genomic instability, one of the many contributory factors to gastric cancer. This article also covers the constraints of incomplete knowledge of epigenetic factors influencing gastric cancer, thus throwing light on our understanding of the disease.
胃癌是一种恶性且具有高度增殖性的疾病，已对全球大量人口产生了重大影响，已知其由多种因素引起，包括遗传、表观遗传和环境影响。尽管这些癌症的全球趋势正在下降，但由于生活方式和饮食习惯的改变，其发病率的上升仍然是一个威胁。然而，与胃癌相关的遗传和表观遗传改变在致癌发展中也有同等的作用。DNA甲基化是表观遗传修饰的主要形式之一，在胃癌发生过程中起着重要作用。甲基化导致一些最重要的基因失活，如DNA修复基因、细胞周期调节因子、凋亡基因、转录调节因子和信号通路调节因子；这随后导致细胞不受控制的增殖。这些基因的突变可作为疾病早期诊断的合适预后标志物，因为胃癌的晚期诊断对患者的总体生存有巨大的负面影响。在这篇综述中，我们关注导致胃癌发生的重要表观遗传突变以及它们各自的分子发病机制。甲基化、乙酰化和组蛋白修饰在基因组不稳定的发生中起着不可或缺的作用，而基因组不稳定是导致胃癌的众多因素之一。本文还涵盖了对影响胃癌的表观遗传因素认识不完整的局限性，从而有助于我们对该疾病的理解。
