Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program.
Hilary A Robbins, Karine Alcala, Elham Khodayari Moez, Florence Guida, Sera Thomas, Hana Zahed, Matthew T Warkentin, Karl Smith-Byrne, Yonathan Brhane, David Muller, Xiaoshuang Feng, Demetrius Albanes, Melinda C Aldrich, Alan A Arslan, Julie Bassett, Christine D Berg, Qiuyin Cai, Chu Chen, Michael P A Davies, Brenda Diergaarde, John K Field, Neal D Freedman, Wen-Yi Huang, Mikael Johansson, Michael Jones, Woon-Puay Koh, Stephen Lam, Qing Lan, Arnulf Langhammer, Linda M Liao, Geoffrey Liu, Reza Malekzadeh, Roger L Milne, Luis M Montuenga, Thomas Rohan, Howard D Sesso, Gianluca Severi, Mahdi Sheikh, Rashmi Sinha, Xiao-Ou Shu, Victoria L Stevens, Martin C Tammem��gi, Lesley F Tinker, Kala Visvanathan, Ying Wang, Renwei Wang, Stephanie J Weinstein, Emily White, David Wilson, Jian-Min Yuan, Xuehong Zhang, Wei Zheng, Christopher I Amos, Paul Brennan, Mattias Johansson, Rayjean J Hung
Author Information
Hilary A Robbins: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: RobbinsH@iarc.fr.
Karine Alcala: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Elham Khodayari Moez: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
Florence Guida: Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Sera Thomas: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
Hana Zahed: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Matthew T Warkentin: Prosserman 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-Byrne: Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
Yonathan Brhane: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada.
David Muller: Division of Genetic Medicine, Imperial College London School of Public Health, London, UK.
Xiaoshuang Feng: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Demetrius Albanes: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Melinda C Aldrich: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Alan A Arslan: Departments of Obstetrics and Gynecology and Population Health, New York University Grossman School of Medicine, New York, NY.
Julie Bassett: Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Christine D Berg: Retired, Bethesda, MD.
Qiuyin Cai: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Chu Chen: Program 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 Davies: Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Brenda Diergaarde: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; UPMC Hillman Cancer Centre, Pittsburgh, PA.
John K Field: Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Neal D Freedman: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Wen-Yi Huang: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Mikael Johansson: Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden.
Michael Jones: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Woon-Puay Koh: Healthy 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 Lam: Integrative Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Qing Lan: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Arnulf Langhammer: HUNT Research Center, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway; Levanger Hospital, Nord-Tr��ndelag Hospital Trust, Levanger, Norway.
Linda M Liao: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Geoffrey Liu: Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, Canada.
Reza Malekzadeh: Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Roger L Milne: Cancer 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 Montuenga: Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain; IDISNA, Pamplona, Spain; CIBERONC, Madrid, Spain.
Thomas Rohan: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
Howard D Sesso: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gianluca Severi: Inserm, Universit�� Paris-Saclay, Villejuif, France.
Mahdi Sheikh: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Rashmi Sinha: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Xiao-Ou Shu: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Victoria L Stevens: Rollins School of Public Health, Emory University, Atlanta, GA.
Martin C Tammem��gi: Department of Health Sciences, Brock University, St. Cathaarines, ON, Canada; Prevention and Cancer Control, Ontario Health, Toronto, ON, Canada.
Lesley F Tinker: Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
Kala Visvanathan: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Ying Wang: American Cancer Society, Atlanta, GA.
Renwei Wang: UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
Stephanie J Weinstein: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Emily White: Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
David Wilson: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Jian-Min Yuan: Department of Epidemiology, Graduate Schoolf of Public Health, University of Pittsburgh, Pittsburgh, PA; UPMC Hillman Cancer Centre, Pittsburgh, PA.
Xuehong Zhang: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Wei Zheng: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Christopher I Amos: Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX.
Paul Brennan: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Mattias Johansson: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: JohanssonM@iarc.fr.
Rayjean J Hung: Prosserman 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.
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.
