整合PRS特异性和年龄特异性变化后，针对风险调整的PSA筛查对前列腺癌的初步影响
Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation
影响因子:2.80000
分区:生物学3区 / 遗传学3区
发表日期:2024
作者:
Xiaomin Liu, Hongyuan Duan, Siwen Liu, Yunmeng Zhang, Yuting Ji, Yacong Zhang, Zhuowei Feng, Jingjing Li, Ya Liu, Ying Gao, Xing Wang, Qing Zhang, Lei Yang, Hongji Dai, Zhangyan Lyu, Fangfang Song, Fengju Song, Yubei Huang
摘要
尽管前列腺癌（PCA）的风险在不同的年龄和遗传风险方面有所不同，但尚不清楚遗传特异性和特定年龄特异性的前列腺特异性抗原（PSA）筛查对PCA的筛查（PCA）。构建了从PLCO试验中，构建了对参与者的构建，以将PCA分类为低或高PRS。 PCA筛选的PSA的年龄特异性和PRS特异性截止值由时间依赖性接收器 - 操作 - 特征曲线和面积下曲线（TDAUC）确定。将PSA的PRS特异性和年龄特异性截止值整合的改进的筛选策略与传统的PSA筛选值与传统的PSA筛选，对准确性，高级PCA的检测率（GLEASEAN评分≥7）和假阳性率。与PCA的80个SNP相对的PRS与PCA显着相关，将其确定为最佳PRS，并确定为0.631的AUC。通过PRS分层后，低PR和高PRS组的PCA风险为10年的PSA的TDAUC分别为0.818和0.816，而截止值分别为1.42和1.62 ng/mL。根据年龄进行进一步分层后，低PRS（1.42、1.65、1.60、1.60和2.24 ng/ml年龄<60、60-64、65-69、65-69和≥70年）的PSA年龄特异性截止值相对较低。进一步的分析显示，阳性PSA和高PR在PCA发生率和死亡率上存在明显的相互作用。在不同年龄和PRS的PSA（ - ）亚组中观察到PCA风险的差异很小，PCA（+）的PCA发病率和死亡率显着增加，因为年龄和PRS的高PRS/PSA（+）的风险最高，年龄≥70岁的参与者[HRS（95％CI）：16.00（95％CI）：16.00（12.62-20.62-20.62-20-20-20-20-20-20.29） （9.26-40.96）]。推荐的筛选策略降低了错过的PCA的12.8％，确保了高特异性，但不会引起过多的假阳性。与传统的PSA筛选相比，危险的筛选集成了PRS特异性和年龄特异性PSA的临界值比传统的PSA筛选更有效。
Abstract
Although the risk of prostate cancer (PCa) varies across different ages and genetic risks, it's unclear about the effects of genetic-specific and age-specific prostate-specific antigen (PSA) screening for PCa.Weighed and unweighted polygenic risk scores (PRS) were constructed to classify the participants from the PLCO trial into low- or high-PRS groups. The age-specific and PRS-specific cut-off values of PSA for PCa screening were determined with time-dependent receiver-operating-characteristic curves and area-under-curves (tdAUCs). Improved screening strategies integrating PRS-specific and age-specific cut-off values of PSA were compared to traditional PSA screening on accuracy, detection rates of high-grade PCa (Gleason score ≥7), and false positive rate.Weighted PRS with 80 SNPs significantly associated with PCa was determined as the optimal PRS, with an AUC of 0.631. After stratifying by PRS, the tdAUCs of PSA with a 10-year risk of PCa were 0.818 and 0.816 for low- and high-PRS groups, whereas the cut-off values were 1.42 and 1.62 ng/mL, respectively. After further stratifying by age, the age-specific cut-off values of PSA were relatively lower for low PRS (1.42, 1.65, 1.60, and 2.24 ng/mL for aged <60, 60-64, 65-69, and ≥70 years) than high PRS (1.48, 1.47, 1.89, and 2.72 ng/mL). Further analyses showed an obvious interaction of positive PSA and high PRS on PCa incidence and mortality. Very small difference in PCa risk were observed among subgroups with PSA (-) across different age and PRS, and PCa incidence and mortality with PSA (+) significantly increased as age and PRS, with highest risk for high-PRS/PSA (+) in participants aged ≥70 years [HRs (95%CI): 16.00 (12.62-20.29) and 19.48 (9.26-40.96)]. The recommended screening strategy reduced 12.8% of missed PCa, ensured high specificity, but not caused excessive false positives than traditional PSA screening.Risk-adapted screening integrating PRS-specific and age-specific cut-off values of PSA would be more effective than traditional PSA screening.