1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai.
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai.
J Natl Compr Canc Netw. 2021 Oct 15;20(1):54-62. doi: 10.6004/jnccn.2021.7010.
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 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.
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.
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.
尽管根据 GLOBOCAN 2020 数据，中国前列腺癌（PCa）新发病例占全球的 7.8%，新死亡病例占全球的 14.5%，但种系突变与 PCa 风险的相关性仍不明确，部分原因是缺乏全国性证据。本研究对 1836 例中国 PCa 患者的 19 个 PCa 易感性基因进行了测序，并评估了与遗传突变相关的疾病风险。
患者来自 4 家三甲癌症中心（n=1160）和一家商业实验室（n=676）。采用多基因panel 对患者的种系 DNA 进行测序，比较了 PCa 患者与 gnomAD（基因组聚合数据库）和 ChinaMAP（中国代谢分析项目）数据库人群中致病性/可能致病性（P/LP）突变频率。根据突变状态评估临床特征和无进展生存期。
来自医院的 1160 例患者中，89.7%的 Gleason 评分为≥8，65.6%有转移。8.49%的中国 PCa 患者发现 P/LP 突变。ATM（比值比[OR]，5.9；95%可信区间[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）和 PALB2（OR，5.9；95%CI，2.7-13.2）突变与 PCa 风险相关。与无突变者相比，ATM、BRCA2、MSH2 或 PALB2 突变患者接受雄激素剥夺治疗和阿比特龙治疗的结局较差（风险比，2.19[95%CI，1.34-3.58]和 2.47[95%CI，1.23-4.96]），但接受多西他赛治疗的获益相似。
本多中心研究证实，中国相当一部分 PCa 患者存在遗传突变，并确定了这一报道较少的人群中的易感基因。这些数据为中国 PCa 患者的精准预防和预后评估提供了经验证据。
