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Design and Methodological Considerations for Biomarker Discovery and Validation in the Integrative Analysis of Lung Cancer Etiology and Risk (Integral) Program Publisher Pubmed



Robbins HA1 ; Alcala K1 ; Moez EK2 ; Guida F3 ; Thomas S2 ; Zahed H1 ; Warkentin MT2, 4 ; Smithbyrne K5 ; Brhane Y2 ; Muller D6 ; Feng X1 ; Albanes D7 ; Aldrich MC8 ; Arslan AA9 Show All Authors
Authors
  1. Robbins HA1
  2. Alcala K1
  3. Moez EK2
  4. Guida F3
  5. Thomas S2
  6. Zahed H1
  7. Warkentin MT2, 4
  8. Smithbyrne K5
  9. Brhane Y2
  10. Muller D6
  11. Feng X1
  12. Albanes D7
  13. Aldrich MC8
  14. Arslan AA9
  15. Bassett J10
  16. Berg CD11
  17. Cai Q12
  18. Chen C13
  19. Davies MPA14
  20. Diergaarde B15, 16
  21. Field JK14
  22. Freedman ND7
  23. Huang WY7
  24. Johansson M17
  25. Jones M18
  26. Koh WP19, 20
  27. Lam S21
  28. Lan Q7
  29. Langhammer A22, 23
  30. Liao LM7
  31. Liu G24
  32. Malekzadeh R25
  33. Milne RL10, 26, 27
  34. Montuenga LM28, 29, 30
  35. Rohan T31
  36. Sesso HD32
  37. Severi G33
  38. Sheikh M1
  39. Sinha R7
  40. Shu XO12
  41. Stevens VL34
  42. Tammemagi MC35, 36
  43. Tinker LF37
  44. Visvanathan K38
  45. Wang Y39
  46. Wang R40
  47. Weinstein SJ7
  48. White E41
  49. Wilson D42
  50. Yuan JM16, 43
  51. Zhang X32
  52. Zheng W12
  53. Amos CI44
  54. Brennan P1
  55. Johansson M17
  56. Hung RJ2, 4
Show Affiliations
Authors Affiliations
  1. 1. Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
  2. 2. Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Canada
  3. 3. Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
  4. 4. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
  5. 5. Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
  6. 6. Division of Genetic Medicine, Imperial College London School of Public Health, London, United Kingdom
  7. 7. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
  8. 8. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  9. 9. Departments of Obstetrics and Gynecology and Population Health, New York University Grossman School of Medicine, New York, NY, United States
  10. 10. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia
  11. 11. Retired, Bethesda, MD
  12. 12. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  13. 13. Program in Epidemiology and the Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  14. 14. Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom
  15. 15. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
  16. 16. UPMC Hillman Cancer Centre, Pittsburgh, PA, United States
  17. 17. Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden
  18. 18. Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom
  19. 19. Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  20. 20. Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
  21. 21. Integrative Oncology, British Columbia Cancer Agency, Vancouver, Canada
  22. 22. HUNT Research Center, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway
  23. 23. Levanger Hospital, Nord-Trondelag Hospital Trust, Levanger, Norway
  24. 24. Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, Canada
  25. 25. Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  26. 26. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia
  27. 27. School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia
  28. 28. Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain
  29. 29. IDISNA, Pamplona, Spain
  30. 30. CIBERONC, Madrid, Spain
  31. 31. Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
  32. 32. Brigham and Women's Hospital, Harvard Medical School, Boston, MA
  33. 33. Inserm, Universite Paris-Saclay, Villejuif, France
  34. 34. Rollins School of Public Health, Emory University, Atlanta, GA
  35. 35. Department of Health Sciences, Brock University, St. Cathaarines, ON, Canada
  36. 36. Prevention and Cancer Control, Ontario Health, Toronto, ON, Canada
  37. 37. Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  38. 38. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
  39. 39. American Cancer Society, Atlanta, GA
  40. 40. UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States
  41. 41. Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  42. 42. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
  43. 43. Department of Epidemiology, Graduate Schoolf of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
  44. 44. Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, United States

Source: Annals of Epidemiology Published:2023


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. © 2022