The Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom.
The Institute of Cancer Research and Royal Marsden National Health Service (NHS) Foundation Trust, Academic Urology Unit and The Oncogenetics Team, London SW3 6JJ, United Kingdom.
Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):a030379. doi: 10.1101/cshperspect.a030379.
Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified. Consistent reports have identified germline mutations in the genes , , , , , and as conferring moderate risks, with some leading to a more aggressive disease behavior. Considering this knowledge, several research strategies have been developed to determine whether targeted prostate screening using genetic information can overcome the limitations of population-based prostate-specific antigen (PSA) screening. Germline DNA-repair mutations are more frequent in men with metastatic disease than previously thought, and these patients have a more favorable response to therapy with poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors. Genomic information is a practical tool that has the potential to enable the concept of precision medicine to become a reality in all steps of PCa patient care.
前列腺癌（PCa）是一种高度遗传性疾病，测序技术的快速发展使我们对其遗传继承有了更深入的了解。目前最被接受的模型是一种复杂的多基因模型，涉及常见的低外显率易感等位基因，这些基因单独引起的风险很小，但累积起来会显著增加风险，以及更罕见的遗传变异，这些变异会导致更大的风险。通过全基因组关联研究，已经确定了 100 多个与 PCa 风险相关的单核苷酸多态性（SNP）。一致的报告已经确定了基因 、 、 、 、 和 中的种系突变赋予中度风险，其中一些导致疾病行为更具侵袭性。考虑到这些知识，已经开发了几种研究策略来确定是否可以使用遗传信息来克服基于人群的前列腺特异性抗原（PSA）筛查的局限性。与以前认为的相比，携带转移疾病的男性中种系 DNA 修复突变更为频繁，这些患者对聚（腺苷二磷酸[ADP]-核糖）聚合酶（PARP）抑制剂的治疗反应更好。基因组信息是一种实用工具，有可能使精准医学的概念在 PCa 患者护理的所有步骤中成为现实。
