Accès ouvert déclaré 2025 article

Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers

Batel Blechter, Xiaoyu Wang, Juncheng Dai, Christiana Karsonaki, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu‐Yu Chen, Rayjean J. Hung, Young Tae Kim, Jacob Williams, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Jiucun Wang, Wei Jie Seow, Lei Song, I‐Shou Chang, Li-Hsin Chien, Qiuyin Cai, Hee Nam Kim, Yi‐Long Wu, Maria Pik Wong, Shilan Li, Tongwu Zhang, Charles E. Breeze, Bryan A. Bassig, Jin Hee Kim, Demetrius Albanes, Jason Yy Wong Sm, Min‐Ho Shin, Lap Ping Chung, Yang Yang, Hong Zheng, Hong Dai, Yasushi Yatabe, Xu‐Chao Zhang, Young‐Chul Kim, Neil E. Caporaso, Jiang Chang, Jcm Ho, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Kenichi Okubo, Takayuki Honda, H. Dean Hosgood, Hideo Kunitoh, Shun-ichi Watanabe, Yohei Miyagi, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Kōichi Goto, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Mitchell J. Machiela, Yeul Hong Kim, In‐Jae Oh, Victor Lee, Gee-Chen Chang, Kuan‐Yu Chen, Wu‐Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Yu‐Tang Gao, Jianjun Liu, Ann G. Schwartz, Richard S. Houlston, Ivan Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardón, Chen Chu, Stig E. Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu‐Tian Ji, H. E. Wichmann, D.C. Christiani, Gad Rennert, Susanne M. Arnold, Paul Brennan, James McKay, John K. Field, Michael P.A. Davies, Sanjay Shete, Loı̈c Le Marchand, Geoffrey Liu, Angeline S. Andrew, Lambertus A. Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Angela Cox, Fiona Taylor, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Hyo‐Sung Jeon, Shih Sheng Jiang, Chung–Hsing Chen, Chin‐Fu Hsiao, Zhibin Hu, Laura Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Sonja I Berndt, Wei Wu, Junwen Wang, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Chang Hyun Kang, Wen‐Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong‐Jen Yu, Gong Yang, Alan Sihoe, Yi Young Choi, In Kyu Park, Hsiao-Han Hung, Roel Vermeulen, Iona Cheng, Junjie Wu, Fang-Yu Tsai, John K. C. Chan, Jihua Li, Hsien-Chih Lin, Jie Liu, Bao‐Liang Song, Norie Sawada, Taiki Yamaji, Hongxia Ma, Meng Zhu, Yifan Wang, T. Y. Qi, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Guoping Wu, Chih‐Yi Chen, Chien-Jen Chen ScD, Pan‐Chyr Yang, Victoria L. Stevens, Joseph F. Fraumeni, Kuang Lin, Robin G. Walters, Zhengming Chen, Olga Y. Gorlova, Christopher I. Amos, Hongbing Shen, Chao A. Hsiung, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan, Haoyu Zhang

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160Institutions déclarées

22Pays d’affiliation déclarés

Résumé fourni par la source

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

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DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers
Date Crossref: 01/10/2025
Éditeur: Oxford University Press (OUP)
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.

Institutions déclarées

National Cancer Institute Division of Cancer Epidemiology and Genetics Jiangsu Cancer Hospital Nanjing Medical University University of Oxford National Cancer Research Institute Kyungpook National University Aichi Cancer Center National Health Research Institutes Tunghai University Lunenfeld-Tanenbaum Research Institute Sinai Health System Tianjin Medical University Cancer Institute and Hospital National Taiwan University Hospital Tianjin Medical University Vanderbilt University Medical Center Chonnam National University Seoul National University Hospital Chonnam National University Hospital Chonnam National University Hwasun Hospital Korea University American Cancer Society Chinese Academy of Medical Sciences & Peking Union Medical College Shenyang Medical College China Medical University First Hospital of China Medical University Fudan University Pharmaceutical Biotechnology (Czechia)University of Hong Kong National University of Singapore National University Health System National Dong Hwa University Seoul National University New Generation University College Guangdong Academy of Medical Sciences Queen Mary Hospital University of North Carolina at Chapel Hill Georgetown University Georgetown University Medical Center St. Jude Children's Research Hospital Inova Health System Sejong University Korea Research Institute of Bioscience and Biotechnology National Heart, Lung, and Blood Institute Shanghai Pulmonary Hospital National Cancer Center Tokyo National Hospital Huazhong University of Science and Technology Shiga University of Medical Science University of Tokyo Hospital RIKEN Center for Integrative Medical Sciences The University of Tokyo Tokyo Medical and Dental University Institute of Science Tokyo Hospital Albert Einstein College of Medicine Japanese Red Cross Medical Center Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center National Cancer Center Hospital East Akita University Saga University Nagoya University Nippon Medical School Shinshu University Fukushima Medical University Fukushima Medical University Hospital Gunma University Hospital Gunma University China National Environmental Monitoring Center National Chung Hsing University Taichung Veterans General Hospital Chung Shan Medical University Hospital Xiamen Chang Gung Hospital Chung Shan Medical University National Cheng Kung University Hospital National Yang Ming Chiao Tung University Taipei Veterans General Hospital Kyungpook National University Medical Center Shanghai Jiao Tong University Renji Hospital Leidos (United States)Shandong Tumor Hospital Shandong First Medical University Genome Institute of Singapore Wayne State University The Barbara Ann Karmanos Cancer Institute Institute of Cancer Research Cancer Genetics (United States)Houston Institute for Clinical Research Communication University of Zhejiang Zhejiang University Mayo Clinic in Arizona BC Cancer Agency Laboratoire d’immunologie intégrative du cancer Universidad de Oviedo Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa University of Taipei Genomics Research Center, Academia Sinica Fred Hutch Cancer Center Academia Sinica University of Copenhagen Gentofte Hospital World Health Organization Centre international de recherche sur le cancer German Cancer Research Center University of Salzburg Heidelberg University German Center for Lung Research Nephrologisches Zentrum Goettingen Zimmer Biomet (Netherlands)Helmholtz Munich Zimmer Biomet (Germany)Ludwig-Maximilians-Universität München Massachusetts Department of Public Health Harvard University Technion – Israel Institute of Technology Markey Cancer Center University of Liverpool The University of Texas MD Anderson Cancer Center University of Hawaiʻi at Mānoa University of Hawaii System Cancer Center of Hawaii University of Hawaii Cancer Center Princess Margaret Cancer Centre Cotton (United States)USC Norris Comprehensive Cancer Center Radboud University Nijmegen Radboud University Medical Center National Institute of Occupational Health Umeå University University of Sheffield UPMC Hillman Cancer Center University of Pittsburgh Medical Center University at Buffalo, State University of New York Moffitt Cancer Center Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. (United States)University of California, San Francisco University of California System Korea University Seoul National University Bundang Hospital Cancer Research Institute Taipei Medical University Liaoning Cancer Hospital & Institute National Hsinchu University of Education Castle Peak Hospital Gleneagles Hospital Utrecht University Shanghai Medical College of Fudan University Zhongshan Hospital Queen Elizabeth Hospital Qujing Normal University Center for Global Health Research Center for Applied Science, Academia Sinica Institute of Sociology, Academia Sinica Johns Hopkins University Johns Hopkins Medicine Baylor College of Medicine Children's Cancer Center New Mexico Cancer Center

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