Inherited Mutations in Chinese Men With Prostate Cancer

Author:

Zhu Yao12,Wei Yu12,Zeng Hao34,Li Yonghong5,Ng Chi-Fai67,Zhou Fangjian5,He Caiyun58,Sun Guangxi34,Ni Yuchao34,Chiu Peter K.F.67,Teoh Jeremy Y.C.67,Wang Beihe12,Pan Jian12,Wan Fangning12,Dai Bo12,Qin Xiaojian12,Lin Guowen12,Gan Hualei19,Wu Junlong12,Ye Dingwei12

Affiliation:

1. 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai;

2. 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai;

3. 3Department of Urology, and

4. 4Institute of Urology, West China Hospital, Sichuan University, Chengdu;

5. 5Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou;

6. 6Department of Surgery, and

7. 7SH Ho Urology Center, Chinese University of Hong Kong, Hong Kong;

8. 8Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou; and

9. 9Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

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.

Publisher

Harborside Press, LLC

Subject

Oncology

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