Oncogenetics Team, Division of Genetics & Epidemiology, The Institute of Cancer Research, Sir Richard Doll Building, 15 Cotswold road, Sutton, SM2 5NG, UK.
Fam Cancer. 2022 Jan;21(1):101-114. doi: 10.1007/s10689-021-00227-3. Epub 2021 Jan 24.
Improvements in DNA sequencing technology and discoveries made by large scale genome-wide association studies have led to enormous insight into the role of genetic variation in prostate cancer risk. High-risk prostate cancer risk predisposition genes exist in addition to common germline variants conferring low-moderate risk, which together account for over a third of familial prostate cancer risk. Identifying men with additional risk factors such as genetic variants or a positive family history is of clinical importance, as men with such risk factors have a higher incidence of prostate cancer with some evidence to suggest diagnosis at a younger age and poorer outcomes. The medical community remains in disagreement on the benefits of a population prostate cancer screening programme reliant on PSA testing. A reduction in mortality has been demonstrated in many studies, but at the cost of significant amounts of overdiagnosis and overtreatment. Developing targeted screening strategies for high-risk men is currently the subject of investigation in a number of prospective studies. At present, approximately 38% of the familial risk of PrCa can be explained based on published SNPs, with men in the top 1% of the risk profile having a 5.71-fold increase in risk of developing cancer compared with controls. With approximately 170 prostate cancer susceptibility loci now identified in European populations, there is scope to explore the clinical utility of genetic testing and genetic-risk scores in prostate cancer screening and risk stratification, with such data in non-European populations eagerly awaited. This review will focus on both the rare and common germline genetic variation involved in hereditary and familial prostate cancer, and discuss ongoing research in exploring the role of targeted screening in this high-risk group of men.
DNA 测序技术的改进和大规模全基因组关联研究的发现，使我们对遗传变异在前列腺癌风险中的作用有了巨大的认识。除了常见的种系变异赋予低-中度风险外，还存在高危前列腺癌风险易感性基因，这些基因共同导致超过三分之一的家族性前列腺癌风险。识别具有遗传变异或阳性家族史等额外风险因素的男性具有临床重要性，因为这些风险因素的男性前列腺癌发病率更高，有一些证据表明发病年龄更早，结局更差。医学界仍然对依赖 PSA 检测的人群前列腺癌筛查计划的益处存在分歧。许多研究表明死亡率有所降低，但代价是大量的过度诊断和过度治疗。目前，许多前瞻性研究正在针对高危男性制定靶向筛查策略。目前，基于已发表的 SNP，大约 38%的前列腺癌家族风险可以得到解释，与对照组相比，风险评分最高的 1%男性患癌症的风险增加了 5.71 倍。在欧洲人群中现已确定了大约 170 个前列腺癌易感性位点，因此有机会探索遗传检测和遗传风险评分在前列腺癌筛查和风险分层中的临床应用，人们急切期待非欧洲人群的相关数据。本文将重点讨论遗传性和家族性前列腺癌中涉及的罕见和常见种系遗传变异，并讨论正在进行的研究，以探索靶向筛查在这一高危男性群体中的作用。
