Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases  

作　　者：Rong Na Dingwei Ye Jun Qi Fang Liu Xiaoling Lin Brian T Helfand Charles B Brendler Carly Conran Jian Gong Yishuo Wu Xu Gao Yaqing Chen S Lilly Zheng Zengnan Mo Qiang Ding Yinghao Sun Jianfeng Xu 

机构地区：[1]Department of Urology, Huashan Hospital, Fudan University, Shanghai, China [2]Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China [3]Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois, USA [4]Health Communication Institute, School of Public Health, Fudan University, Shanghai, China [5]Department of Urology, Shanghai Cancer Center, Fudan University, Shanghai, China [6]Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China [7]Division of Urology, NorthShore University HealthSystem, Evanston, Illinois, USA [8]Department of Urology, Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China [9]Department of Medical Ultrasonic, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China [10]Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China

出　　处：《Asian Journal of Andrology》2016年第4期525-529,共5页亚洲男性学杂志（英文版）

基　　金：This work was in part supported by grants from the Key Project of the National Science Foundation of China to Jianfeng Xu （81130047）, the National Key Basic Research Program Grant 973 of China to Jianfeng Xu （2012CB518301）, the National Natural Science Foundation of China （Grant No. 81402339） to Rong Na, the intramural grants from Huashan Hospital Fudan University to Rong Na. This study is also partially supported by the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem to JX. Finally, We would like to thank all the subjects included in this study.

摘　　要：Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.

关 键 词：Chinese genetic risk score genome-wide association study prostate cancer single nucleotide polymorphism 

分 类 号：TP391.41[自动化与计算机技术—计算机应用技术] Q959.53[自动化与计算机技术—计算机科学与技术]