ArticleAnnals of epidemiology2023
Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program.
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Article in Annals of epidemiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 29 citations in OpenAlex.
- Epigenetic Profiling for Early Detection and Treatment Response Monitoring in Non-Small Cell Lung Cancer: Protocol for a Prospective Translational Biomarker Study.JMIR research protocols · 2026Article
- From evidence to action: the IARC's role in strengthening cancer prevention and early detection.Journal of the National Cancer Institute. Monographs · 2026Review
- From Lung Cancer Predictive Models toJournal of clinical medicine · 2026Review
- Advances in the Basic Sciences in Thoracic Oncology in the Last 20 Years and Their Translational Impact.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Advances and challenges in circulating tumor DNA-based early detection of lung cancer.Translational cancer research · 2025Review
- The Associations of Air Pollution Mixture Exposure with Plasma Proteins in an Elderly U.S. Panel.Environmental science & technology · 2025Article
- Association between socioeconomic position and lung cancer incidence in 16 countries: a prospective cohort consortium study.EClinicalMedicine · 2025Article
- Lightweight Advanced Deep Neural Network (DNN) Model for Early-Stage Lung Cancer Detection.Diagnostics (Basel, Switzerland) · 2024Article
- Protein Biomarkers in Lung Cancer Screening: Technical Considerations and Feasibility Assessment.Archivos de bronconeumologia · 2024Review
- Non-small-cell lung cancer.Nature reviews. Disease primers · 2024Review
- Evaluation of risk prediction models to select lung cancer screening participants in Europe: a prospective cohort consortium analysis.The Lancet. Digital health · 2024Article
- Retrospective evaluation of plasma protein tumour markers for early lung cancer detection.BJC reports · 2024Article
- Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank.Nature communications · 2024Article
- Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.Nature communications · 2024Article
- Lung Cancer Risk Prediction Models for Asian Ever-Smokers.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Review
- Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools.Journal of the National Cancer Institute · 2023Article
- Circulating proteome for pulmonary nodule malignancy.Journal of the National Cancer Institute · 2023Article
- Liquid Biopsy in NSCLC: An Investigation with Multiple Clinical Implications.International journal of molecular sciences · 2023Review
- ATR-FTIR Spectroscopy with Chemometrics for Analysis of Saliva Samples Obtained in a Lung-Cancer-Screening Programme: Application of Swabs as a Paradigm for High Throughput in a Clinical Setting.Journal of personalized medicine · 2023Article
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Authors and funding
56 authors at 20 institutions in 10 countries.
Hilary A RobbinsGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: RobbinsH@iarc.fr.
Karine AlcalaGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Elham Khodayari MoezProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
Florence GuidaEnvironment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Sera ThomasProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
Hana ZahedGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Matthew T WarkentinProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Karl Smith-ByrneCancer Epidemiology Unit, University of Oxford, Oxford, UK.
Yonathan BrhaneProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
David MullerDivision of Genetic Medicine, Imperial College London School of Public Health, London, UK.
Xiaoshuang FengGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Melinda C AldrichDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Alan A ArslanDepartments of Obstetrics and Gynecology and Population Health, New York University Grossman School of Medicine, New York, NY.
Julie BassettCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Christine D BergRetired, Bethesda, MD.
Qiuyin CaiDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Chu ChenProgram in Epidemiology and the Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Michael P A DaviesMolecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Brenda DiergaardeDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; UPMC Hillman Cancer Centre, Pittsburgh, PA.
John K FieldMolecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Neal D FreedmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Mikael JohanssonDepartment of Radiation Sciences, Oncology, Umea University, Umea, Sweden.
Michael JonesDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Woon-Puay KohHealthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
Stephen LamIntegrative Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Qing LanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Arnulf LanghammerHUNT Research Center, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Linda M LiaoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Geoffrey LiuComputational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, Canada.
Reza MalekzadehDigestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia; School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.
Luis M MontuengaCenter of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain; IDISNA, Pamplona, Spain; CIBERONC, Madrid, Spain.
Thomas RohanDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
Howard D SessoBrigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gianluca SeveriInserm, Université Paris-Saclay, Villejuif, France.
Mahdi SheikhGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Rashmi SinhaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Victoria L StevensRollins School of Public Health, Emory University, Atlanta, GA.
Martin C TammemägiDepartment of Health Sciences, Brock University, St. Cathaarines, ON, Canada; Prevention and Cancer Control, Ontario Health, Toronto, ON, Canada.
Lesley F TinkerWomen's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Ying WangAmerican Cancer Society, Atlanta, GA.
Renwei WangUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
Stephanie J WeinsteinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Emily WhiteCancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
David WilsonDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Jian-Min YuanDepartment of Epidemiology, Graduate Schoolf of Public Health, University of Pittsburgh, Pittsburgh, PA; UPMC Hillman Cancer Centre, Pittsburgh, PA.
Xuehong ZhangBrigham and Women's Hospital, Harvard Medical School, Boston, MA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX.
Paul BrennanGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Mattias JohanssonGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: JohanssonM@iarc.fr.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Electronic address: Rayjean.hung@lunenfeld.ca.
Centre international de recherche sur le cancer · FRNational Cancer Institute · USUPMC Hillman Cancer Center · USAmerican Cancer Society · USBrigham and Women's Hospital · USLunenfeld-Tanenbaum Research Institute · CAVanderbilt University Medical Center · USAgency for Science, Technology and Research · SGAlbert Einstein College of Medicine · USFred Hutch Cancer Center · USUniversity of Liverpool · GBUniversity of Pittsburgh · USUniversity of Toronto · CABaylor College of Medicine · USCancer Council Victoria · AUEmory University · USImperial College London · GBInserm · FRInstitute of Cancer Research · GBJohns Hopkins University · US
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI MICHELLE A RUDEK · 1985 to 2026
$208.6MVECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dan Paul Zandberg · 1988 to 2026
$158.0MWOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0MVitamin D3 Modulation of Inflammation and Lung Cancer RiskP50CA090440 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SIEGFRIED, JILL M · 2001 to 2015
$34.6MWomen's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2MTranslating Molecular and Clinical Data to Population Lung Cancer Risk AssessmentU19CA203654 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Mattias Alexander Johansson · 2017 to 2026
$23.7MSouthern Community Cohort StudyU01CA202979 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLOT, WILLIAM J., SHRUBSOLE, MARTHA J. · 2016 to 2025
$22.0MPhysicians' Health Study II: Prevention Trial of VitaminsR01CA097193 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GAZIANO, J. MICHAEL · 2002 to 2011
$15.7MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0MWomen's Health Study: Continued Follow-UpR01HL080467 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E. · 2005 to 2010
$4.5MCancer Research UK 29017NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA090440NCI NIH HHS R01 CA034944NCI NIH HHS R01 CA040360NCI NIH HHS R01 CA047988NCI NIH HHS R01 CA097193NCI NIH HHS R01 CA251758NCI NIH HHS R03 CA245979NCI NIH HHS U01 CA086308NCI NIH HHS U01 CA182913NCI NIH HHS U01 CA202979NCI NIH HHS U19 CA203654NCI NIH HHS UM1 CA182913NEI NIH HHS R01 EY018820NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS R01 HL026490NHLBI NIH HHS R01 HL034595NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL080467NHLBI NIH HHS RC1 HL099355NIA NIH HHS U01 AG018033WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005World Health Organization 001
Abstract
The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.
Indexed as
Lung NeoplasmsBiomarkersCase-Control StudiesCohort StudiesEarly Detection of CancerHumansLungProspective StudiesTomography, X-Ray ComputedBiomarkersbiomarker discovery and validationbiomarkersearly detectionLung cancer screeningnodule malignancyrisk predictionstudy design
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