Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis
Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis
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DOI：
10.1016/j.eururo.2020.11.014
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发表时间：
2021-02-11
期刊：
影响因子：
23.4
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
--
作者：
Shi, Zhuqing;Platz, Elizabeth A.;Xu, Jianfeng
背景：基于单核苷酸多态的遗传风险评分(GRS)已被开发并验证用于前列腺癌(PCa)风险评估。由于GRS是人群标准化的，它的值可以被解释为相对于普通人群的相对风险。目的：比较GRS与指南推荐的两种遗传风险指标--家族史(FH)和罕见致病突变(RPM)--在预测PCa发病率和死亡率方面的表现。设计、背景和参与者：一个前瞻性队列来自UK Biobbank，其中208 685名无PCa诊断的参与者在招募时通过英国癌症和死亡登记进行跟踪。结果测量和统计分析：FH(阳性与阴性)、RPM(携带者与非携带者)的PCa发生率和死亡率的比率(RRS)，结果和局限性：经过9.67年的中位随访期，共鉴定出6890例PCa事件(419例死于PCa)。在单变量分析中，这三个指标均与前列腺癌的发病率显著相关；RR(95%可信区间[CI])值FH为1.88(1.75-2.01)，RPM为2.89(1.89-4.25)，GRS为1.97(1.87-2.07)(均P<；0.001)。在多变量分析中，这些关联是独立的。虽然FH和RPM确定了11%的男性有较高的前列腺癌风险，但添加GRS发现了另外22%的男性有较高的前列腺癌风险，并且C-统计量在区分发病率(p<；0.001)和区分死亡率(p=0.002)方面从0.58%增加到0.67%。结论：这项基于人群的前瞻性研究表明，GRS补充了指南推荐的两种遗传风险指标(FH和RPM)，用于对前列腺癌的发病率和死亡率进行分层。患者概述：在一项来自英国Biobank的大型基于人群的前列腺癌(PCA)前瞻性研究中，遗传风险评分(GRS)补充了指南推荐的两种遗传风险指标(家族病史和罕见致病突变)，以预测前列腺癌的发病率和死亡率。这些结果为将GRS纳入PCA风险评估提供了关键数据。(C)2020年欧洲泌尿外科协会。爱思唯尔出版，版权所有。
Background: Single nucleotide polymorphism-based genetic risk score (GRS) has been developed and validated for prostate cancer (PCa) risk assessment. As GRS is population standardized, its value can be interpreted as a relative risk to the general population.Objective: To compare the performance of GRS with two guideline-recommended inherited risk measures, family history (FH) and rare pathogenic mutations (RPMs), for predicting PCa incidence and mortality.Design, setting, and participants: A prospective cohort was derived from the UK Biobank where 208 685 PCa diagnosis-free participants at recruitment were followed via the UK cancer and death registries.Outcome measurements and statistical analysis: Rate ratios (RRs) of PCa incidence and mortality for FH (positive vs negative), RPMs (carriers vs noncarriers), and GRS (top vs bottom quartile) were measured.Results and limitations: After a median follow-up of 9.67 yr, 6890 incident PCa cases (419 died of PCa) were identified. Each of the three measures was significantly associated with PCa incidence in univariate analyses; RR (95 % confidence interval [CI]) values were 1.88 (1.75-2.01) for FH, 2.89 (1.89-4.25) for RPMs, and 1.97(1.87-2.07) for GRS (all p < 0.001). The associations were independent in multivariable analyses. While FH and RPMs identified 11 % of men at higher PCa risk, addition of GRS identified an additional 22 % of men at higher PCa risk, and increases in C-statistic from 0.58 to 0.67 for differentiating incidence (p < 0.001) and from 0.65 to 0.71 for differentiating mortality (p = 0.002). Limitations were a small number of minority patients and short mortality follow-up.Conclusions: This population-based prospective study suggests that GRS complements two guideline-recommended inherited risk measures (FH and RPMs) for stratifying the risk of PCa incidence and mortality.Patient summary: In a large population-based prostate cancer (PCa) prospective study derived from UK Biobank, genetic risk score (GRS) complements two guideline-recommended inherited risk measures (family history and rare pathogenic mutations) in predicting PCa incidence and mortality. These results provide critical data for including GRS in PCa risk assessment. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.