Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai, China
Baijun Dong , Bin Yang , Yonghong Li , Wei Chen , Jing Li , Zhenzhou Xu , Kaijie Wu , Fengbo Zhang , Shimiao Zhu , Lu Yi , Lixin Hua , Hao PAN , Hong Ma , Zhongquan Sun , Huihua Cheng , Zhenting Zhang , Mingzhao Li , Zhiwen Chen , Fangqin Wang , Wei Xue
Background: Philadelphia Prostate Cancer Consensus Conference 2017 developed an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA. However, the consensus was mainly based on data from Caucasian populations. Genetic differences in the PC molecular landscape between Asian and Caucasian men have been established. Whether Caucasian-based genetic information can be used to guide clinical practice in Chinese population needs further evidence. Methods: 1123 patients with confirmed prostate cancer admitted from March 2018 to August 2019 from 18 Chinese centers were included in this retrospective study. We sequenced the association of 50 gene with prostate cancer risk, clinical treatment implications and predisposition, focusing on DNA repair gene and genetic susceptibility genes pathogenic mutations in Philadelphia Prostate Cancer Consensus Conference. Only protein-truncating alterations (nonsense/stop-gains, frameshift insertions and deletions, and donor and acceptor splice-site mutations) were coded as pathogenic or likely pathogenic protein-truncating alterations. Results: Among all cases, DNA repair gene pathogenic mutations were found in 133 men (11.84%), including BRCA2 (62 [5.5%]), ATM (15 [1.3%]), PALB2 (11 [0.97%]), GEN1 (7 [0.62%]), BRCA1 (6 [0.53%]), MLH3 (4 [0.35%]), MUTYH (4 [0.35%]), PMS1 (4 [0.35%]), RAD50 (4 [0.35%]), ATR (3 [0.27%]), CHEK2 (3 [0.27%]), FANCD2 (3 [0.27%]) etc. Similar germline DRG mutation frequencies were observed between our cohort and Caucasian men. Noticeably, G84E mutation in HOXB13, a rare but recurrent missense mutation associated with a significantly increased risk of hereditary prostate cancer was not found in our cohort of patients. Furthermore, the frequency of HSD3B1 (1245C) allele in the Chinese patients is much lower than that in the Caucasian populations (11.7% vs 63%). Conclusions: Our study retrospectively analyzed germline mutation profile of prostate cancer in Chinese population. The frequency of HSD3B1 (1245C) allele varies across ethnic populations in spite of the similar DNA repair gene mutations rates. Considering the gene list should be tested based on clinical/familial scenarios from the Philadelphia Prostate Cancer Consensus Conference, a prevalence of certain mutations, G84E mutation in HOXB13 was unnecessary for genetic testing in Chinese population.
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