文章：

前列腺癌的后全基因组关联分析：从遗传关联到生物学贡献

Post-GWAS in prostate cancer: from genetic association to biological contribution

原文发布日期：2018-12-11

DOI: 10.1038/s41568-018-0087-3

类型: Review Article

开放获取: 否

英文摘要：

Genome-wide association studies (GWAS) have been successful in deciphering the genetic component of predisposition to many human complex diseases including prostate cancer. Germline variants identified by GWAS progressively unravelled the substantial knowledge gap concerning prostate cancer heritability. With the beginning of the post-GWAS era, more and more studies reveal that, in addition to their value as risk markers, germline variants can exert active roles in prostate oncogenesis. Consequently, current research efforts focus on exploring the biological mechanisms underlying specific susceptibility loci known as causal variants by applying novel and precise analytical methods to available GWAS data. Results obtained from these post-GWAS analyses have highlighted the potential of exploiting prostate cancer risk-associated germline variants to identify new gene networks and signalling pathways involved in prostate tumorigenesis. In this Review, we describe the molecular basis of several important prostate cancer-causal variants with an emphasis on using post-GWAS analysis to gain insight into cancer aetiology. In addition to discussing the current status of post-GWAS studies, we also summarize the main molecular mechanisms of potential causal variants at prostate cancer risk loci and explore the major challenges in moving from association to functional studies and their implication in clinical translation.

摘要翻译： 

全基因组关联研究（GWAS）在解析包括前列腺癌在内的多种人类复杂疾病遗传易感性方面取得了显著成就。通过GWAS鉴定的种系变异逐步填补了关于前列腺癌遗传性的重要认知空白。随着后GWAS时代的开启，越来越多研究揭示，种系变异不仅可作为风险标志物，更在前列腺癌发生过程中发挥积极作用。当前研究重点集中于应用新颖精准的分析方法，基于现有GWAS数据探索特定易感位点（即因果变异）的生物学机制。这些后GWAS分析成果凸显了利用前列腺癌风险相关种系变异识别参与前列腺肿瘤发生的新基因网络和信号通路的潜力。本文综述中，我们详细阐述了几种重要前列腺癌因果变异的分子基础，重点探讨如何运用后GWAS分析深入理解癌症病因学。在论述后GWAS研究现状的同时，我们亦总结了前列腺癌风险位点潜在因果变异的主要分子机制，探究从关联研究到功能研究转型过程中的重大挑战及其临床转化意义。

原文链接：

Post-GWAS in prostate cancer: from genetic association to biological contribution