利用单核苷酸多态性和前列腺特异性抗原预测前列腺癌风险

Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen.

作者信息

Li-Sheng Chen Sam, Ching-Yuan Fann Jean, Sipeky Csilla, Yang Teng-Kai, Yueh-Hsia Chiu Sherry, Ming-Fang Yen Amy, Laitinen Virpi, Tammela Teuvo L J, Stenman Ulf-Håkan, Auvinen Anssi, Schleutker Johanna, Chen Hsiu-Hsi

机构信息

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University , Taipei.

Department of Health Industry Management, School of Healthcare Management, Kainan University , Tao-Yuan , Taiwan.

出版信息

J Urol. 2019 Mar;201(3):486-495. doi: 10.1016/j.juro.2018.10.015.

DOI:10.1016/j.juro.2018.10.015

PMID:30366021

Abstract

PURPOSE

Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information.

MATERIALS AND METHODS

We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above.

RESULTS

The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined.

CONCLUSIONS

Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.

摘要

目的

单核苷酸多态性与前列腺特异性抗原的综合信息为通过风险分层提高筛查性能提供了机会。我们旨在基于前列腺特异性抗原以及单核苷酸多态性信息预测前列腺癌风险。

材料与方法

我们对20575名接受前列腺特异性抗原检测的男性以及4967名基于来自芬兰前列腺癌人群筛查试验的66个单核苷酸多态性和来自芬兰前列腺癌DNA研究的7个单核苷酸多态性的5269个样本进行前列腺癌多基因风险评分的男性进行了一项前瞻性研究。构建了一个贝叶斯预测模型，在仅限于前列腺特异性抗原为4 ng/ml或更高的研究对象中，将遗传信息与前列腺特异性抗原依次结合，以估计前列腺癌风险，并与仅使用前列腺特异性抗原进行比较。

结果

基于7个单核苷酸多态性以及前列腺特异性抗原水平的前列腺癌后验概率在4 ng/ml时为3.7，6 ng/ml时为14.2，8至9 ng/ml时为40.7，10 ng/ml时为98.2。与仅使用前列腺特异性抗原时的70.1%（95%可信区间69.6 - 70.7）相比，前列腺特异性抗原与基于7个单核苷酸多态性的风险评分相结合时，ROC曲线下面积提高到88.8%（95%可信区间88.6 - 89.1）。当所有前列腺癌易感多基因结合时，该面积进一步升至96.7%（95%可信区间96.5 - 96.9）。