A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening

被引:0
作者
Yong-Qiao He
Tong-Min Wang
Mingfang Ji
Zhi-Ming Mai
Minzhong Tang
Ruozheng Wang
Yifeng Zhou
Yuming Zheng
Ruowen Xiao
Dawei Yang
Ziyi Wu
Changmi Deng
Jiangbo Zhang
Wenqiong Xue
Siqi Dong
Jiyun Zhan
Yonglin Cai
Fugui Li
Biaohua Wu
Ying Liao
Ting Zhou
Meiqi Zheng
Yijing Jia
Danhua Li
Lianjing Cao
Leilei Yuan
Wenli Zhang
Luting Luo
Xiating Tong
Yanxia Wu
Xizhao Li
Peifen Zhang
Xiaohui Zheng
Shaodan Zhang
Yezhu Hu
Weiling Qin
Bisen Deng
Xuejun Liang
Peiwen Fan
Yaning Feng
Jia Song
Shang-Hang Xie
Ellen T. Chang
Zhe Zhang
Guangwu Huang
Miao Xu
Lin Feng
Guangfu Jin
Jinxin Bei
Sumei Cao
机构
[1] Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy
[2] Zhongshan Hospital of Sun Yat-sen University,Cancer Research Institute of Zhongshan City
[3] The University of Hong Kong,School of Public Health
[4] The University of Hong Kong,Center for Nasopharyngeal Carcinoma Research (CNPCR)
[5] National Cancer Institute,Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics
[6] National Institutes of Health,Key Laboratory of Cancer Immunotherapy and Radiotherapy
[7] Wuzhou Red Cross Hospital,Department of Genetics
[8] Wuzhou Cancer Center,School of Public Health
[9] Chinese Academy of Medical Sciences,State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Departments of Institute for Cancer Research
[10] Medical College of Soochow University,Departments of Institute for Cancer Research
[11] Sun Yat-sen University,Department of Otolaryngology
[12] Public Health Service Center of Xiaolan Town,Head and Neck Surgery
[13] The Third Affiliated Hospital of Xinjiang Medical University,Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collabor
[14] Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region,Division of Infection and Immunity
[15] The Third Affiliated Teaching Hospital of Xinjiang Medical University,Department of Nasopharyngeal Carcinoma, Sun Yat
[16] Affiliated Cancer Hospital,sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
[17] Center for Health Sciences,Department of Radiation Oncology, Sun Yat
[18] Exponent,sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
[19] Inc.,Human Genetics, Genome Institute of Singapore
[20] Stanford Cancer Institute,Department of Medicine
[21] First Affiliated Hospital of Guangxi Medical University,Department of Clinical Oncology
[22] Nanjing Medical University,Clinical Effectiveness Group
[23] Faculty of Medical Sciences - University College London,Department of Medical Epidemiology and Biostatistics
[24] International Agency for Research on Cancer (IARC/WHO),Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer
[25] Sun Yat-sen University Cancer Center,undefined
[26] Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,undefined
[27] Agency for Science,undefined
[28] Technology and Research (A*STAR),undefined
[29] Yong Loo Lin School of Medicine,undefined
[30] National University of Singapore,undefined
[31] The University of Hong Kong,undefined
[32] Institute of Health and Society,undefined
[33] University of Oslo,undefined
[34] Karolinska Institutet,undefined
[35] Fujian Medical University,undefined
来源
Nature Communications | / 13卷
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摘要
Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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