Prostate cancer susceptibility is a polygenic trait. We aimed to examine the controversial diagnostic utility of single-nucleotide polymorphisms (SNP) for prostate cancer. We analyzed two datasets collected from Europeans and one from Africans. These datasets were generated by the genome-wide association studies, that is, CGEMS, BPC3, and MEC-Africans, respectively. About 540,000 SNPs, including 61 risk markers that constitute a panel termed MK-61, were commonly genotyped. For each dataset, we augmented the MK-61 panel to generate an MK-61+ one by adding several thousands of SNPs that were moderately associated with prostate cancer occurrence in external dataset(s). We assessed the diagnostic utility of both panels by measuring their predictive strength for prostate cancer occurrence with AUC statistics. We calculated the theoretical AUCs using quantitative genetics model-based formulae and obtained the empirical estimates via 10-fold cross-validation using statistical and machine learning techniques. For the MK-61 panel, the 95% confidence intervals of the theoretical AUCs (AUC-CI.95) were 0.578–0.655, 0.596–0.656, and 0.539–0.596 in the CGEMS, BPC3, and MEC-Africans cohorts, respectively. For the MK-61+ panels, the corresponding AUC-CI.95 were 0.617–0.663, 0.527–0.736, and 0.547–0.565. The empirical AUCs largely fell within the theoretical interval. A promising result (AUC = 0.703, FNR = 0.354, FPR = 0.353) was obtained in the BPC3 cohort when the MK-61+ panel was used. In the CGEMS cohort, the MK-61+ panel complemented PSA in predicting the disease status of PSA ≥ 2.0 ng/mL samples. This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with ![Formula][1]ng/mL. Prevention Relevance: This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with PSA ≥ 2 ng/mL. [1]: /embed/tex-math-1.gif

中文翻译：

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多个队列数据集的综合分析破译了生殖系单核苷酸多态性在前列腺癌诊断中的效用

前列腺癌易感性是一种多基因性状。我们旨在检查单核苷酸多态性 (SNP) 对前列腺癌的有争议的诊断效用。我们分析了从欧洲人和非洲人收集的两个数据集。这些数据集分别由全基因组关联研究生成，即 CGEMS、BPC3 和 MEC-Africans。大约 540,000 个 SNP，包括构成称为 MK-61 的面板的 61 个风险标记，通常进行基因分型。对于每个数据集，我们通过在外部数据集中添加数千个与前列腺癌发生中度相关的 SNP 来增强 MK-61 面板以生成 MK-61+ 面板。我们通过使用 AUC 统计测量它们对前列腺癌发生的预测强度来评估这两个组的诊断效用。我们使用基于数量遗传学模型的公式计算了理论 AUC，并使用统计和机器学习技术通过 10 倍交叉验证获得了经验估计。对于 MK-61 小组，CGEMS、BPC3 和 MEC-Africans 队列的理论 AUC (AUC-CI.95) 的 95% 置信区间分别为 0.578–0.655、0.596–0.656 和 0.539–0.596。对于 MK-61+ 组，相应的 AUC-CI.95 为 0.617–0.663、0.527–0.736 和 0.547–0.565。经验 AUC 很大程度上落在理论区间内。当使用 MK-61+ 组时，在 BPC3 队列中获得了有希望的结果（AUC = 0.703，FNR = 0.354，FPR = 0.353）。在 CGEMS 队列中，MK-61+ 小组在预测 PSA ≥ 2.0 ng/mL 样本的疾病状态方面补充了 PSA。这项研究表明，风险增加的 SNP 面板可以增强对欧洲血统男性的前列腺癌预测，尤其是那些具有 ![Formula][1]ng/mL 的男性。预防相关性：本研究表明，风险增加的 SNP 面板可以增强欧洲血统男性的前列腺癌预测，尤其是那些 PSA ≥ 2 ng/mL 的男性。[1]：/embed/tex-math-1.gif