Inherited Mutations in Chinese Men With Prostate Cancer

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  • 1 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai;
  • | 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai;
  • | 3 Department of Urology, and
  • | 4 Institute of Urology, West China Hospital, Sichuan University, Chengdu;
  • | 5 Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou;
  • | 6 Department of Surgery, and
  • | 7 SH Ho Urology Center, Chinese University of Hong Kong, Hong Kong;
  • | 8 Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou; and
  • | 9 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

Submitted October 8, 2020; final revision received January 15, 2021; accepted for publication January 15, 2021. Published online October 15, 2021.

Author contributions: Study concept: Zhu. Data curation: Wei, Sun, Ni, Qin, Wu. Formal analysis: Zhou, He, Chiu, Teoh, Wang, Pan, Wan, Dai, Lin, Gan. Funding acquisition: Zhu. Investigation: Zeng, Li, Ng. Methodology: Zhu, Zhou, He, Chiu, Teoh, Wan, Dai, Gan. Resources: Zhu, Zeng, Li, Ng. Supervision: Zhu, Wu, Ye. Validation: Wang, Pan, Lin. Visualization: Wei, Zeng, Li, Ng, Wu. Writing – original draft: Wei, Zeng, Li, Ng, Wu. Writing – review and editing: Zhu, Ye.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by the National Natural Science Foundation of China (grants 81972375 [Y. Zhu], 81902568 [J. Wu]), Shanghai Rising Star Program (grant 16QA1401100 [Y. Zhu]), Shanghai “Rising Stars of Medical Talent” Youth Development Program, the General Program of Beijing Xisike Clinical Oncology Research Foundation (grant Y-2019AZMS-0012 [Y. Zhu]), and Shanghai Anti-Cancer Association Eyas Project (grant SACA-CY19A01 [Y. Wei]). The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.

Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Correspondence: Yao Zhu, MD, Department of Urology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai 200032, China. Email: yaozhu09@fudan.edu.cn; Junlong Wu, MD, Department of Urology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai 200032, China. Email: wujunlong920601@163.com; and Dingwei Ye, MD, Department of Urology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai 200032, China. Email: dwye.shca@gmail.com

Supplementary Materials

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