ArticleJournal of the National Cancer Institute2025
Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.
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- Prognostic and immunotherapeutic implications of histamine-related biomarkers in lung adenocarcinoma.PeerJ · 2026Article
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197 authors.
Batel BlechterDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Xiaoyu WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Juncheng DaiDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Christiana KarsonakiNuffield Department of Population Health, University of Oxford, Oxford, UK.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Kouya ShiraishiDivision of Genome Biology, National Cancer Research Institute, Tokyo, Japan.
Jiyeon ChoiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Keitaro MatsuoDivision of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tzu-Yu ChenInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
Kexin ChenDepartment of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases of the Ministry of Education, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Young Tae KimDepartment of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Parichoy Pal ChoudhuryAmerican Cancer Society, Atlanta, GA, USA.
Jacob WilliamsDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Dongxin LinDepartment of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Zhihua YinDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
Baosen ZhouDepartment of Clinical Epidemiology and Center of Evidence Based Medicine, The First Hospital of China Medical University, Shenyang, China.
Jiucun WangMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Wei Jie SeowSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Lei SongDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
I-Shou ChangNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
Wei HuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Li-Hsin ChienInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Qiuyin CaiDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Yun-Chul HongDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hee Nam KimDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Yi-Long WuGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Maria Pik WongDepartment of Pathology, Queen Mary Hospital, Hong Kong, China.
Brian Douglas RichardsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Shilan LiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Charles BreezeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Zhaoming WangDepartment of Epidemiology and Cancer Control (Primary) & Department of Computational Biology (Secondary), St Jude Children's Research Hospital, Memphis, TN, USA.
Bryan A BassigSaville Cancer Screening and Prevention Center, Inova Schar Cancer Institute, Inova Health System, Fairfax, VA, USA.
Jin Hee KimDepartment of Integrative Bioscience & Biotechnology, Institute of Bioscience, Sejong University, Seoul, 05006, Republic of Korea.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Jason Yy Wong SmEpidemiology and Community Health Branch, National Heart Lung and Blood Institute, Bethesda, MD, USA.
Min-Ho ShinDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Lap Ping ChungDepartment of Pathology, Queen Mary Hospital, Hong Kong, China.
Yang YangShanghai Pulmonary Hospital, Shanghai, China.
Hong ZhengDepartment of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases of the Ministry of Education, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Hongji DaiDepartment of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases of the Ministry of Education, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Yasushi YatabeDepartment of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
Xu-Chao ZhangGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Young-Chul KimLung Cancer Clinic, Pulmonary Medicine, Chonnam National University Medical School, Hwasun Hospital, Hwasun, Republic of Korea.
Neil E CaporasoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Jiang ChangSchool of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
James Chung Man HoDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Yataro DaigoCenter for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yukihide MomozawaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Yoichiro KamataniLaboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Masashi KobayashiDepartment of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Kenichi OkuboDepartment of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Takayuki HondaDepartment of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
H Dean HosgoodDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, USA.
Hideo KunitohDepartment of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
Shun-Ichi WatanabeDepartment of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
Yohei MiyagiMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Shingo MatsumotoDepartment of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Hidehito HorinouchiDepartment of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
Masahiro TsuboiDepartment of Thoracic Oncology, Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
Ryuji HamamotoDivision of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo, Japan.
Koichi GotoDepartment of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Atsushi TakahashiRIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Japan, Yokohama.
Akiteru GotoDepartment of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
Yoshihiro MinamiyaDepartment of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita, Japan.
Megumi HaraDepartment of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Yuichiro NishidaDepartment of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Kenji TakeuchiDepartment of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kenji WakaiDepartment of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Koichi MatsudaLaboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Yoshinori MurakamiDepartment of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan.
Kimihiro ShimizuDivision of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine Asahi, Nagano, Japan.
Hiroyuki SuzukiDepartment of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
Motonobu SaitoDepartment of Cancer Genome Medicine, Fukushima Medical University Hospital, Fukushima, Japan.
Yoichi OhtakiDepartment of Integrative center of General Surgery, Gunma University Hospital, Gunma, Japan.
Kazumi TanakaDepartment of Healthcare Quality and Safety, Gunma University Graduate School of Medicine, Gunma, Japan.
Tangchun WuDept of Occupational and Environmental Health, Key Laboratory for Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Fusheng WeiChina National Environmental Monitoring Center, Beijing, China.
Mitchell J MachielaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Yeul Hong KimKorea University College of Medicine Anam Hospital, Seoul, Republic of Korea.
In-Jae OhLung Cancer Center, Chonnam National University Hwasun Hospital, Hwasuneup, Republic of Korea.
Victor Ho Fun LeeDepartment of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Gee-Chen ChangSchool of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Kuan-Yu ChenDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Wu-Chou SuDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yuh-Min ChenDepartment of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Adeline SeowSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Jae Yong ParkLung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
Sun-Seog KweonDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Yu-Tang GaoDepartment of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Jianjun LiuLab of Human Genomics, Genome Institute of Singapore, A*STAR, Singapore, Singapore.
Ann G SchwartzKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Richard HoulstonDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Ivan P GorlovDepartment of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational Research, Houston, TX, USA.
Xifeng WuSchool of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Ping YangDepartment of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
Stephen LamDepartment of Integrative Oncology, BC Cancer, Vancouver, BC, Canada.
Adonina TardonHealth Research Institute of Asturias (ISPA), IUOPA University of Oviedo and University Nebrija, Spain.
Chu ChenProgram in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Stig E BojesenDepartment Of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mattias JohanssonInternational Agency for Research on Cancer (IARC/WHO), Lyon, France.
Angela RischGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Heike BickeböllerUniversity Medical Center Goettingen, Goettingen, Germany.
Bu-Tian JiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
H-Erich WichmannInstitute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.
David C ChristianiHarvard TH Chan School of Public Health, Boston, MA, USA.
Gad RennertTechnion-Israel Institute of Technology and APRPM, Haifa, Israel.
Susanne M ArnoldMarkey Cancer Center, Lexington, KY, USA.
Paul BrennanInternational Agency for Research on Cancer (IARC/WHO), Lyon, France.
James McKayInternational Agency for Research on Cancer (IARC/WHO), Lyon, France.
John K FieldUniversity of Liverpool, Liverpool, UK.
Michael P A DaviesUniversity of Liverpool, Liverpool, UK.
Sanjay S SheteThe University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Loïc Le MarchandEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Geoffrey LiuPrincess Margaret Cancer Center, Toronto, ON, Canada.
Angeline S AndrewNorris Cotton Cancer Center, Lebanon, NH, USA.
Lambertus A KiemeneyRadboud University Medical Center, Nijmegen, The Netherlands.
Shan Zienolddiny-NaruiNational Institute of Occupational Health, Oslo, Norway.
Kjell GrankvistDepartment of Medical Biosciences, Umeå University, Umeå, Sweden.
Angela CoxDivision of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
Fiona TaylorUniversity of Sheffield, Sheffield, UK.
Jian-Min YuanUPMC Hillman Cancer Center and Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Philip LazarusDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, SUNY University at Buffalo, NY, USA.
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Melinda C AldrichDepartment of Medicine, Division of Genetic Medicine and Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
Hyo-Sung JeonCancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
Shih Sheng JiangNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
Chung-Hsing ChenNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
Chin-Fu HsiaoInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Zhibin HuDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Laura BurdettDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Meredith YeagerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Amy HutchinsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Belynda HicksDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Jia LiuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Wei WuDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
Junwen WangDivision of Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
Yuqing LiDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA, San Francisco.
Jin Eun ChoiDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Kyong Hwa ParkDepartment of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
Sook Whan SungDepartment of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Chang Hyun KangDepartment of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Wen-Chang WangThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Jun XuSchool of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Peng GuanDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
Wen TanDepartment of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chong-Jen YuDepartment of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
Gong YangDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Alan Dart Loon SihoeGleneagles Hong Kong Hospital, Hong Kong, China.
Yi Young ChoiCancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
In Kyu ParkDepartment of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hsiao-Han HungNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
Roel C H VermeulenDivision of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
Iona ChengDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA, San Francisco.
Junjie WuDepartment of Pulmonary and Critical Care Medicine Zhongshan Hospital, Fudan University Shanghai Geriatric Medical Center, Shanghai, China.
Fang-Yu TsaiNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
John K C ChanDepartment of Pathology, Queen Elizabeth Hospital, Hong Kong, China.
Jihua LiQujing Center for Diseases Control and Prevention, Qujing, China.
Hsien-Chih LinInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Jie LiuDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China.
Bao SongDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China.
Norie SawadaDivision of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
Taiki YamajiDivision of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
Kathleen WyattDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Hongxia MaDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Meng ZhuDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Yifan WangDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Tianchen QiDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Xuelian LiDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
Yangwu RenDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
Ann ChaoCenter for Global Health, National Cancer Institute, Bethesda, MD, USA.
Motoki IwasakiDivision of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
Junjie ZhuShanghai Pulmonary Hospital, Shanghai, China.
Guoping WuChina National Environmental Monitoring Center, Beijing, China.
Chih-Yi ChenInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Chien-Jen Chen ScDGenomic Research Center, Academia Sinica, Taipei, Taiwan.
Pan-Chyr YangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Victoria L StevensLaboratory Services, American Cancer Society, Georgia, USA.
Joseph F FraumeniDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Kuang LinNuffield Department of Population Health, University of Oxford, Oxford, UK.
Robin G WaltersNuffield Department of Population Health, University of Oxford, Oxford, UK.
Zhengming ChenNuffield Department of Population Health, University of Oxford, Oxford, UK.
Nilanjan ChatterjeeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Olga Y GorlovaInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Hongbing ShenDepartment of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Chao Agnes HsiungInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Takashi KohnoDivision of Genome Biology, National Cancer Research Institute, Tokyo, Japan.
Qing LanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Haoyu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Funding
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5MTHE CAROTENE AND RETINOL EFFICACY TRIAL (CARET)U01CA063673 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOODMAN, GARY E · 1994 to 2006
$13.0MTransdisciplinary Research in Cancer of the Lung (TRICL)U19CA148127 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AMOS, CHRISTOPHER I., LE MARCHAND, LOIC · 2010 to 2014
$10.9MPROSTATE, LUNG, COLORECTAL, &OVARIAN CANCER SCREENINGN01CN025476 · CN · WESTAT, INC. · PI O'BRIEN, BARBARA B · 1992 to 2000
$7.9MProspective studies of cancer etiology and prevention in Shanghai and SingaporeR01CA144034 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YUAN, JIAN-MIN · 2010 to 2014
$7.0MShanghai Womens Health StudyUM1CA182910 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZHENG, WEI · 2014 to 2018
$5.9MTHE SINGAPORE COHORT STUDY OF DIET AND CANCERR01CA080205 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YUAN, JIAN-MIN · 1999 to 2009
$5.3MCancer Risk Reduction and Diet: A Cohort Study of WomenR37CA070867 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZHENG, WEI · 2009 to 2013
$4.7MA genomewide study of lung cancer in never smokersR01CA149462 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GORLOVA, OLGA · 2010 to 2014
$4.4MCancer epidemiology cohorts in Shanghai and Singapore UM1CA182876 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YUAN, JIAN-MIN · 2014 to 2018
$4.3MOvercoming acquired resistance to EGFR inhibitors in lung cancerR01CA121210 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LOVLY, CHRISTINE M. · 2007 to 2016
$2.9MInfrastructure Support and Pilot Tissue Collection for the CARET BiorepositoryU01CA167462 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEUHOUSER, MARIAN L · 2018 to 2022
$2.9MCCR NIH HHS N01 RC037004Intramural NIH HHS Z99 CA999999NCI NIH HHS N01 CN025404NCI NIH HHS N01 CN025476NCI NIH HHS N01 CN025511NCI NIH HHS N01 CN025512NCI NIH HHS N01 CN025514NCI NIH HHS N01 CN025515NCI NIH HHS N01 CN025516NCI NIH HHS N01 CN025522NCI NIH HHS N01 CN045165NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA080205NCI NIH HHS R01 CA121210NCI NIH HHS R01 CA144034NCI NIH HHS R01 CA149462NCI NIH HHS R01 CA231141NCI NIH HHS R37 CA070867NCI NIH HHS U01 CA063673NCI NIH HHS U01 CA167462NCI NIH HHS U01 CA182876NCI NIH HHS U19 CA148127NCI NIH HHS UM1 CA167462NCI NIH HHS UM1 CA182876NCI NIH HHS UM1 CA182910World Health Organization 001
Abstract
backgroundLung 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.
methodsPRSs 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.
resultsThe 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.
conclusionsMulti-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.
Indexed as
East Asian never smokersGenome-wide association studiesLifetime absolute riskLung adenocarcinomaPolygenic risk scores
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