The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy
To date, the combined effect of polygenic risk score (PRS) and prostate health index (<i>phi</i>) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2...
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MDPI AG
2023-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/4/1343 |
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| author | Xiaohao Ruan Da Huang Jingyi Huang Jinlun Huang Yongle Zhan Yishuo Wu Qiang Ding Danfeng Xu Haowen Jiang Wei Xue Rong Na |
| author_facet | Xiaohao Ruan Da Huang Jingyi Huang Jinlun Huang Yongle Zhan Yishuo Wu Qiang Ding Danfeng Xu Haowen Jiang Wei Xue Rong Na |
| author_sort | Xiaohao Ruan |
| collection | DOAJ |
| description | To date, the combined effect of polygenic risk score (PRS) and prostate health index (<i>phi</i>) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34–2.56), 2.07 (95%CI: 1.50–2.84), 3.26 (95%CI: 2.36–4.48), and 5.06 (95%CI: 3.68–6.97) times as likely to develop PCa (all <i>p</i> < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2–10 ng/mL or 2–20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (<i>phi</i>) at 27–36 (<i>P</i><sub>trend</sub> < 0.05) or >36 (<i>P</i><sub>trend</sub> ≤ 0.001). Notably, men with moderate <i>phi</i> (27–36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high <i>phi</i> (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, <i>phi</i>, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887–0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over <i>phi</i> for PCa. The combination of PRS and <i>phi</i> that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA. |
| first_indexed | 2024-03-11T08:38:42Z |
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| language | English |
| last_indexed | 2024-03-11T08:38:42Z |
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| spelling | doaj.art-6dc8ebdb946d42248ad56dadacc340d02023-11-16T21:18:14ZengMDPI AGJournal of Clinical Medicine2077-03832023-02-01124134310.3390/jcm12041343The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate BiopsyXiaohao Ruan0Da Huang1Jingyi Huang2Jinlun Huang3Yongle Zhan4Yishuo Wu5Qiang Ding6Danfeng Xu7Haowen Jiang8Wei Xue9Rong Na10Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDivision of Urology, Department of Surgery, The University of Hong Kong, Hong Kong, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDivision of Urology, Department of Surgery, The University of Hong Kong, Hong Kong, ChinaTo date, the combined effect of polygenic risk score (PRS) and prostate health index (<i>phi</i>) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34–2.56), 2.07 (95%CI: 1.50–2.84), 3.26 (95%CI: 2.36–4.48), and 5.06 (95%CI: 3.68–6.97) times as likely to develop PCa (all <i>p</i> < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2–10 ng/mL or 2–20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (<i>phi</i>) at 27–36 (<i>P</i><sub>trend</sub> < 0.05) or >36 (<i>P</i><sub>trend</sub> ≤ 0.001). Notably, men with moderate <i>phi</i> (27–36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high <i>phi</i> (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, <i>phi</i>, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887–0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over <i>phi</i> for PCa. The combination of PRS and <i>phi</i> that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA.https://www.mdpi.com/2077-0383/12/4/1343polygenic risk scoreprostate biopsyprostate cancerprostate health indexprostate-specific antigen |
| spellingShingle | Xiaohao Ruan Da Huang Jingyi Huang Jinlun Huang Yongle Zhan Yishuo Wu Qiang Ding Danfeng Xu Haowen Jiang Wei Xue Rong Na The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy Journal of Clinical Medicine polygenic risk score prostate biopsy prostate cancer prostate health index prostate-specific antigen |
| title | The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy |
| title_full | The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy |
| title_fullStr | The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy |
| title_full_unstemmed | The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy |
| title_short | The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy |
| title_sort | combined effect of polygenic risk score and prostate health index in chinese men undergoing prostate biopsy |
| topic | polygenic risk score prostate biopsy prostate cancer prostate health index prostate-specific antigen |
| url | https://www.mdpi.com/2077-0383/12/4/1343 |
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