TY - JOUR
T1 - Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program
AU - Robbins, Hilary A.
AU - Alcala, Karine
AU - Moez, Elham Khodayari
AU - Guida, Florence
AU - Thomas, Sera
AU - Zahed, Hana
AU - Warkentin, Matthew T.
AU - Smith-Byrne, Karl
AU - Brhane, Yonathan
AU - Muller, David
AU - Feng, Xiaoshuang
AU - Albanes, Demetrius
AU - Aldrich, Melinda C.
AU - Arslan, Alan A.
AU - Bassett, Julie
AU - Berg, Christine D.
AU - Cai, Qiuyin
AU - Chen, Chu
AU - Davies, Michael P.A.
AU - Diergaarde, Brenda
AU - Field, John K.
AU - Freedman, Neal D.
AU - Huang, Wen Yi
AU - Johansson, Mikael
AU - Jones, Michael
AU - Koh, Woon Puay
AU - Lam, Stephen
AU - Lan, Qing
AU - Langhammer, Arnulf
AU - Liao, Linda M.
AU - Liu, Geoffrey
AU - Malekzadeh, Reza
AU - Milne, Roger L.
AU - Montuenga, Luis M.
AU - Rohan, Thomas
AU - Sesso, Howard D.
AU - Severi, Gianluca
AU - Sheikh, Mahdi
AU - Sinha, Rashmi
AU - Shu, Xiao Ou
AU - Stevens, Victoria L.
AU - Tammemägi, Martin C.
AU - Tinker, Lesley F.
AU - Visvanathan, Kala
AU - Wang, Ying
AU - Wang, Renwei
AU - Weinstein, Stephanie J.
AU - White, Emily
AU - Wilson, David
AU - Yuan, Jian Min
AU - Zhang, Xuehong
AU - Zheng, Wei
AU - Amos, Christopher I.
AU - Brennan, Paul
AU - Johansson, Mattias
AU - Hung, Rayjean J.
N1 - Funding Information:
This study was supported by the US NCI (INTEGRAL program U19 CA203654 and R03 CA245979), the Lung Cancer Research Foundation, l'Institut National Du Cancer (2019–1-TABAC-01, INCa, France), the Cancer Research Foundation of Northern Sweden (AMP19–962), and an early detection of cancer development grant from Swedish Department of Health ministry. RJH is supported by the Canada Research Chair of the Canadian Institute of Health Research. LMM was supported by FIMA, Fundación ARECES, ISCIII-Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (PI19/00098) and a grant from The Lung Ambition Alliance. MCA is supported by NCI R01 CA251758. The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The Southern Community Cohort Study was supported by NCI U01CA202979. The Physicians’ Health Study (PHS) is supported by research grants CA097193, CA34944, CA40360, HL26490, and HL34595 from the NIH. The Women's Health Study (WHS) is supported by research grants EY06633, EY18820, CA047988, HL043851, HL080467, HL099355, and CA182913 from the NIH.The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. CLUE II funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network; P30 CA006973), National Institute on Aging (U01 AG18033), and the American Institute for Cancer Research. Maryland Cancer Registry (MCR) Cancer data was provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund. The collection and availability of cancer registry data is also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Acknowledgements for the NIH-AARP study are available at: https://dietandhealth.cancer.gov/acknowledgement.html . PLuSS was supported by NCI P50 CA090440 and NCI P30 CA047904.
Funding Information:
This study was supported by the US NCI (INTEGRAL program U19 CA203654 and R03 CA245979), the Lung Cancer Research Foundation, l'Institut National Du Cancer (2019–1-TABAC-01, INCa, France), the Cancer Research Foundation of Northern Sweden (AMP19–962), and an early detection of cancer development grant from Swedish Department of Health ministry. RJH is supported by the Canada Research Chair of the Canadian Institute of Health Research. LMM was supported by FIMA, Fundación ARECES, ISCIII-Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (PI19/00098) and a grant from The Lung Ambition Alliance. MCA is supported by NCI R01 CA251758. The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The Southern Community Cohort Study was supported by NCI U01CA202979. The Physicians’ Health Study (PHS) is supported by research grants CA097193, CA34944, CA40360, HL26490, and HL34595 from the NIH. The Women's Health Study (WHS) is supported by research grants EY06633, EY18820, CA047988, HL043851, HL080467, HL099355, and CA182913 from the NIH.The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. CLUE II funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network; P30 CA006973), National Institute on Aging (U01 AG18033), and the American Institute for Cancer Research. Maryland Cancer Registry (MCR) Cancer data was provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund. The collection and availability of cancer registry data is also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Acknowledgements for the NIH-AARP study are available at: https://dietandhealth.cancer.gov/acknowledgement.html. PLuSS was supported by NCI P50 CA090440 and NCI P30 CA047904. Researchers who are interested in analyzing the Lung Cancer Cohort Consortium (LC3) dataset are encouraged to contact Dr Robbins or Dr Johansson. The LC3 Access Policy is available at the following link: https://www.iarc.who.int/wp-content/uploads/2021/12/LC3_Access_Policy.pdf. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer / World Health Organization. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. ☆ Dr Montuenga reports the following potential conflicts of interest: Astra-Zeneca (speaker's bureau and research grant), Bristol Myers Squibb (research grant), AMADIX: (licensed patent co-holder on complement fragments for lung cancer early detection). All other authors report no conflicts of interest.
Publisher Copyright:
© 2022
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Lung cancer screening
KW - biomarker discovery and validation
KW - biomarkers
KW - early detection
KW - nodule malignancy
KW - risk prediction
KW - study design
UR - http://www.scopus.com/inward/record.url?scp=85141982446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141982446&partnerID=8YFLogxK
U2 - 10.1016/j.annepidem.2022.10.014
DO - 10.1016/j.annepidem.2022.10.014
M3 - Article
C2 - 36404465
AN - SCOPUS:85141982446
VL - 77
SP - 1
EP - 12
JO - Annals of Epidemiology
JF - Annals of Epidemiology
SN - 1047-2797
ER -
