Prognostic evaluation of polygenic risk score underlying pan-cancer analysis: evidence from two large-scale cohorts

被引:6
|
作者
Xin, Junyi [1 ]
Jiang, Xia [2 ,3 ]
Li, Huiqin [1 ,4 ]
Chen, Silu [1 ,5 ]
Zhang, Zhengdong [1 ,5 ]
Wang, Meilin [1 ,5 ]
Gu, Dongying [6 ]
Du, Mulong [4 ,7 ]
Christiani, David C. [7 ,8 ]
机构
[1] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Dept Environm Genom, Jiangsu Key Lab Canc Biomarkers Prevent & Treatmen, Nanjing, Peoples R China
[2] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Stockholm, Sweden
[3] Sichuan Univ, West China Hosp 4, West China Sch Publ Hlth, Dept Epidemiol & Biostat, Chengdu, Peoples R China
[4] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, Nanjing, Peoples R China
[5] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Genet Toxicol,Key Lab Modern Toxicol,Minist E, Nanjing, Peoples R China
[6] Nanjing Med Univ, Nanjing Hosp 1, Dept Oncol, Nanjing, Peoples R China
[7] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth & Epidemiol, 665 Huntington Ave, Boston, MA USA
[8] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA USA
来源
EBIOMEDICINE | 2023年 / 89卷
基金
中国国家自然科学基金;
关键词
Polygenic risk score; Cancer; Survival evaluation; Cohort study; Epidemiology; SURVIVAL; RESOURCE;
D O I
10.1016/j.ebiom.2023.104454
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Polygenic risk score (PRS) has been demonstrated to be effective in identifying individuals at high risk of developing cancer, but its prognostic value remains unclear.Methods We constructed site-specific PRSs by aggregating the risk effect of independent variants derived from previous genome-wide association studies (GWASs) across 17 cancer types. The Cox proportional hazards model was used to evaluate the association of each PRS with cancer survival, leveraging data from two prospective European cohorts, namely the UK Biobank involving 19,628 incident cases and The Cancer Genome Atlas involving 7079 prevalent cases. The combined PRS (CPRS), determined by merging site-specific PRSs, was further used to assess the prognostic effect of PRS on overall cancer in a sex-specific manner.Findings We discovered that the cancer risk-related PRS was associated with neither overall survival (OS) nor cancer -specific survival (CSS) of each site-specific cancer with an underlying false discovery rate (FDR) P > 0.05, as evidenced by consistent findings from the two cohorts. Furthermore, the fixed-effect meta-analysis of the two cohorts provided no evidence to support for an association between CPRS and overall cancer survival in both males [OS: hazard ratio (HR)(meta)= 1.00, P-meta = 0.760; CSS: HRmeta = 1.01, P-meta = 0.447] and females (OS: HRmeta= 0.97, P-meta = 0.067; CSS: HRmeta = 0.96, P-meta = 0.054). Similar results were observed across multiple sensitivity analyses.Interpretation Our findings indicate that the risk-specific PRS might not be a clinically useful tool in cancer prognosis prediction and further studies focusing on the development of polygenic prognostic score are warranted.
引用
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页数:8
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