Section of Urology, Department of Surgery, University of Chicago Medicine, Chicago, IL.
Division of Urology, Department of Surgery, NorthShore University Health System, Evanston, IL.
Clin Chem. 2019 Jan;65(1):74-79. doi: 10.1373/clinchem.2018.286658. Epub 2018 Nov 20.
Prostate cancer (PCa) remains the most common solid malignancy in men, and its prevalence makes understanding its heritability of paramount importance. To date, the most common factors used to estimate a man's risk of developing PCa are age, race, and family history. Despite recent advances in its utility in multiple malignancies (e.g., breast and colon cancer), genetic testing is still relatively underutilized in PCa.
Multiple highly penetrant genes (HPGs) and single-nucleotide polymorphisms (SNPs) have been show to increase a patient's risk of developing PCa. Mutations in the former, like DNA damage repair genes, can confer a 2- to 3-fold increased risk of developing PCa and can increase the risk of aggressive disease. Similarly, PCa-risk SNPs can be used to create risk scores (e.g., genetic or polygenic risk scores) that can be used to further stratify an individual's disease susceptibility. Specifically, these genetic risk scores can provide more specific estimates of a man's lifetime risk ranging up to >6-fold higher risk of PCa.
It is becoming increasingly evident that in addition to the standard family history and race information, it is necessary to obtain genetic testing (including an assessment of HPG mutation status and genetic risk score) to provide a full risk assessment. The additional information derived thereby will improve current practices in PCa screening by risk-stratifying patients before initial prostate-specific antigen testing, determining a patient's frequency of visits, and even help identify potentially at-risk family members.
前列腺癌（PCa）仍然是男性最常见的实体恶性肿瘤，其发病率使得了解其遗传性至关重要。迄今为止，用于估计男性患 PCa 风险的最常见因素是年龄、种族和家族史。尽管最近在多种恶性肿瘤（如乳腺癌和结肠癌）中的应用取得了进展，但遗传检测在 PCa 中的应用仍然相对不足。
已经发现多种高外显率基因（HPG）和单核苷酸多态性（SNP）会增加患者患 PCa 的风险。前者（如 DNA 损伤修复基因）的突变可使患 PCa 的风险增加 2-3 倍，并增加疾病侵袭性的风险。同样，PCa 风险 SNP 可用于创建风险评分（例如，遗传或多基因风险评分），以进一步分层个体的疾病易感性。具体来说，这些遗传风险评分可以提供更具体的男性终生风险估计，风险高达高出 6 倍以上。
越来越明显的是，除了标准的家族史和种族信息外，还需要进行基因检测（包括 HPG 突变状态和遗传风险评分评估），以提供全面的风险评估。由此获得的额外信息将通过在初始前列腺特异性抗原检测前对患者进行风险分层、确定患者的就诊频率，甚至帮助识别潜在高危家族成员，从而改善当前的 PCa 筛查实践。
