Saunders Edward J, Kote-Jarai Zsofia, Eeles Rosalind A
The Institute of Cancer Research, London SM2 5NG, UK.
Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Cancers (Basel). 2021 Feb 12;13(4):760. doi: 10.3390/cancers13040760.
Prostate cancer (PrCa) is a heterogeneous disease, which presents in individual patients across a diverse phenotypic spectrum ranging from indolent to fatal forms. No robust biomarkers are currently available to enable routine screening for PrCa or to distinguish clinically significant forms, therefore late stage identification of advanced disease and overdiagnosis plus overtreatment of insignificant disease both remain areas of concern in healthcare provision. PrCa has a substantial heritable component, and technological advances since the completion of the Human Genome Project have facilitated improved identification of inherited genetic factors influencing susceptibility to development of the disease within families and populations. These genetic markers hold promise to enable improved understanding of the biological mechanisms underpinning PrCa development, facilitate genetically informed PrCa screening programmes and guide appropriate treatment provision. However, insight remains largely lacking regarding many aspects of their manifestation; especially in relation to genes associated with aggressive phenotypes, risk factors in non-European populations and appropriate approaches to enable accurate stratification of higher and lower risk individuals. This review discusses the methodology used in the elucidation of genetic loci, genes and individual causal variants responsible for modulating PrCa susceptibility; the current state of understanding of the allelic spectrum contributing to PrCa risk; and prospective future translational applications of these discoveries in the developing eras of genomics and personalised medicine.
前列腺癌（PrCa）是一种异质性疾病，在个体患者中表现出从惰性到致命形式的多种表型谱。目前尚无可靠的生物标志物可用于前列腺癌的常规筛查或区分具有临床意义的类型，因此晚期疾病的识别以及对无意义疾病的过度诊断和过度治疗仍是医疗保健领域关注的问题。前列腺癌具有很大的遗传成分，自人类基因组计划完成以来的技术进步促进了对影响家庭和人群中该疾病易感性的遗传因素的更好识别。这些遗传标记有望增进对前列腺癌发生的生物学机制的理解，促进基于遗传信息的前列腺癌筛查计划，并指导适当的治疗。然而，在其表现的许多方面仍缺乏深入了解；特别是与侵袭性表型相关的基因、非欧洲人群的风险因素以及对高风险和低风险个体进行准确分层的适当方法。本综述讨论了用于阐明调节前列腺癌易感性的遗传位点、基因和个体因果变异的方法；对导致前列腺癌风险的等位基因谱的当前理解状态；以及这些发现在基因组学和个性化医学发展时代的未来潜在转化应用。
