Insulin-like Growth Factors, Their Binding Proteins, and Prostate Cancer Risk: Analysis of Individual Patient Data from 12 Prospective Studies

  1. Andrew W. Roddam, DPhil;
  2. Naomi E. Allen, DPhil;
  3. Paul Appleby, MSc;
  4. Timothy J. Key, DPhil;
  5. Luigi Ferrucci, MD;
  6. H. Ballentine Carter, MD;
  7. E. Jeffrey Metter, MD;
  8. Chu Chen, PhD;
  9. Noel S. Weiss, MD;
  10. Annette Fitzpatrick, PhD;
  11. Ann W. Hsing, PhD;
  12. James V. Lacey, Jr, PhD;
  13. Kathy Helzlsouer, MD;
  14. Sabina Rinaldi, PhD;
  15. Elio Riboli, MD;
  16. Rudolf Kaaks, PhD;
  17. Joop A.M.J.L. Janssen, MD;
  18. Mark F. Wildhagen, PhD;
  19. Fritz H. Schröder, MD;
  20. Elizabeth A. Platz, ScD;
  21. Michael Pollak, MD;
  22. Edward Giovannucci, MD;
  23. Catherine Schaefer, PhD;
  24. Charles P. Quesenberry, Jr., PhD;
  25. Joseph H. Vogelman, DEE;
  26. Gianluca Severi, PhD;
  27. Dallas R. English, PhD;
  28. Graham G. Giles, PhD;
  29. Pär Stattin, MD;
  30. Göran Hallmans, MD;
  31. Mattias Johansson, PhD;
  32. June M. Chan, ScD;
  33. Peter Gann, MD;
  34. Steven E. Oliver, PhD;
  35. Jeff M. Holly, PhD;
  36. Jenny Donovan, PhD;
  37. François Meyer, MD;
  38. Isabelle Bairati, MD; and
  39. Galan, MD
  1. From University of Oxford, Oxford, United Kingdom; National Institute on Aging, Harbor Hospital, Johns Hopkins University, and Mercy Medical Center, Baltimore, Maryland; Fred Hutchinson Cancer Research Center, Health Sciences, and Collaborative Health Studies Coordinating Center, Seattle, Washington; National Cancer Institute, Bethesda, Maryland; International Agency for Research on Cancer, Lyon Cedex, France; German National Cancer Center, Heidelberg, Germany; Imperial College London, London, United Kingdom; Erasmus MC, Rotterdam, the Netherlands; Cancer Prevention Research Unit, Jewish General Hospital–Lady Davis Institute, Montreal, Canada; Centre de Recherche en Cancérologie, Université Laval, Québec, Canada; Harvard School of Public Health, Boston, Massachusetts; Kaiser Division of Research, Oakland, California; Orentreich Foundation for the Advancement of Science, Cold Spring, New York; Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia; Umeå University, Umeå, Sweden; University of California, San Francisco, San Francisco, California; Northwestern University, Feinberg School of Medicine, Chicago, Illinois; University of York, The Hull York Medical School, Heslington, York, United Kingdom; University of Bristol, Paul O'Gorman Lifeline Centre, Southmead Hospital, Bristol, United Kingdom; and UMR SMBH Université, Bobigny Cedex, France.

    Abstract

    Background: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.

    Purpose: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.

    Data Sources: Studies identified in PubMed, Web of Science, and CancerLit.

    Study Selection: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.

    Data Extraction: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.

    Data Synthesis: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.

    Limitations: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.

    Conclusion: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

    Article and Author Information

    • Grant Support: The central pooling and analysis of these data were supported by Cancer Research UK, London, United Kingdom.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Roddam (e-mail, mailto:andrew.roddam{at}ceu.ox.ac.uk). Data set: Not available.

    • Requests for Single Reprints: Andrew W. Roddam, DPhil, Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom; e-mail, andrew.roddam{at}ceu.ox.ac.uk.

    • Current Author Addresses: Drs. Roddam, Allen, and Key and Mr. Appleby: Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom.

    • Drs. Ferrucci and Metter: Clinical Research Branch, National Institute on Aging, Harbor Hospital, 3001 Hanover Street, Baltimore, MD 21225.

    • Dr. Carter: Johns Hopkins Hospital, Urology–Marburg 145, 600 North Wolfe Street, Baltimore, MD 21287.

    • Dr. Chen: Program in Epidemiology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024.

    • Dr. Weiss: Box 357236, Department of Epidemiology, 1959 NE Pacific Street, Health Sciences F-262D, Seattle, WA 98195.

    • Dr. Fitzpatrick: Box 354922, Collaborative Health Studies Coordinating Center, 6200 NE 74th Street, Suite 310, Building 29, Seattle, WA 98155.

    • Dr. Hsing: Division of Cancer Epidemiology and Genetics, Executive Plaza South, Room 5024, National Cancer Institute, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335.

    • Dr. Lacey: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, MSC 7234, Bethesda, MD 20852-7234.

    • Dr. Helzlsouer: Prevention and Research Center, Mercy Medical Center, 227 Saint Paul Place, Baltimore, MD 21202.

    • Dr. Rinaldi: International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.

    • Dr. Riboli: Division of Epidemiology, Public Health and Primary Care, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.

    • Dr. Kaaks: Division of Cancer Epidemiology, German National Cancer Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

    • Dr. Janssen: Erasmus MC, Department of Internal Medicine, 's Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.

    • Dr. Wildhagen: Erasmus MC, Departments of Urology and Obstetrics & Gynaecology, 's Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.

    • Dr. Schröder: Department of Urology, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands.

    • Dr. Platz: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E6132, Baltimore, MD 21205.

    • Dr. Pollak: Cancer Prevention Research Unit, Jewish General Hospital–Lady Davis Institute, Pollak Research Lab–E 423, 3755 Côte Ste Catherine Road, Montreal, Quebec H3T 1E2, Canada.

    • Dr. Giovannucci: Department of Nutrition and Epidemiology, Harvard School of Public Health, 655 Huntington Avenue, Building II Room 319, Boston, MA 02115.

    • Drs. Schaefer and Quesenberry: Kaiser Division of Research, 2000 Broadway, Oakland CA, 94612.

    • Dr. Vogelman: Orentreich Foundation for the Advancement of Science, Cold Spring, NY 10516.

    • Drs. Severi, English, and Giles: Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton, Victoria 3053, Australia.

    • Drs. Stattin and Johansson: Department of Surgical and Perioperative Sciences Urology and Andrology, Umeå University, 901 85 Umeå, Sweden.

    • Dr. Hallmans: Department of Clinical Medicine and Public Health, Umeå University, 901 85 Umeå, Sweden.

    • Dr. Chan: Epidemiology & Biostatistics, and Urology, University of California, San Francisco, Box 1695, San Francisco, CA 94143-1695.

    • Dr. Gann: Northwestern University, Feinberg School of Medicine, Department of Preventive Medicine, 680 North Lake Shore Drive, Suite 1102, Chicago, IL 60611.

    • Dr. Oliver: Department of Health Sciences, University of York, The Hull York Medical School, Seebohm Rowntree Building, Heslington, York YO10 5DD, United Kingdom.

    • Dr. Holly: Department of Clinical Science at North Bristol, University of Bristol, Paul O'Gorman Lifeline Centre, Southmead Hospital, Bristol BS10 5NB, United Kingdom.

    • Dr. Donovan: Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Clifton, Bristol BS8 2PR, United Kingdom.

    • Drs. Meyer and Bairati: Centre de Recherche en Cancérologie, Université Laval, 11 côte du Palais, Québec G1R 2J6, Canada.

    • Dr. Galan: UMR U557 Inserm, U1125 Inra, Cnam, Paris 13, SMBH— Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France.

    • Author Contributions: Conception and design: A.W. Roddam, N.E. Allen, T.J. Key, C. Chen.

    • Analysis and interpretation of the data: A.W. Roddam, P. Appleby, T.J. Key, C. Chen, M. Pollak.

    • Drafting of the article: A.W. Roddam, N.E. Allen, P. Appleby.

    • Critical revision of the article for important intellectual content: N.E. Allen, T.J. Key, C. Chen, N.S. Weiss, S. Rinaldi, R. Kaaks, J.A.M.J.L. Janssen, M.F. Wildhagen, E.A. Platz, E. Giovannucci, C. Schaefer, C.P. Quesenberry, J.H. Vogelman, G. Severi, D.R. English, G.G. Giles, P. Stattin, M. Johansson, J.M. Chan, P. Gann, S.E. Oliver, J.M. Holly, F. Meyer, I. Bairati.

    • Final approval of the article: A.W. Roddam, N.E. Allen, P. Appleby, T.J. Key, H.B. Carter, C. Chen, N.S. Weiss, A. Fitzpatrick, S. Rinaldi, R. Kaaks, J.A.M.J.L. Janssen, M.F. Wildhagen, E.A. Platz, M. Pollak, E. Giovannucci, C. Schaefer, C.P. Quesenberry, J.H. Vogelman, G. Severi, D.R. English, G.G. Giles, P. Stattin, M. Johansson, J.M. Chan, P. Gann, S.E. Oliver, J.M. Holly, J. Donovan, F. Meyer, I. Bairati.

    • Provision of study materials or patients: N.E. Allen, T.J. Key, C. Chen, N.S. Weiss, A. Fitzpatrick, S. Rinaldi, R. Kaaks, J.A.M.J.L. Janssen, M.F. Wildhagen, E.A. Platz, E. Giovannucci, C. Schaefer, C.P. Quesenberry, J.H. Vogelman, G. Severi, D.R. English, G.G. Giles, P. Stattin, M. Johansson, J.M. Chan, P. Gann, S.E. Oliver, J.M. Holly, J. Donovan, F. Meyer, I. Bairati.

    • Statistical expertise: A.W. Roddam, N.E. Allen, P. Appleby, D.R. English.

    • Obtaining of funding: A.W. Roddam, N.E. Allen, T.J. Key, C. Chen, N.S. Weiss, S. Rinaldi, R. Kaaks, J.A.M.J.L. Janssen, E.A. Platz, E. Giovannucci, C. Schaefer, C.P. Quesenberry, J.H. Vogelman, G. Severi, D.R. English, G.G. Giles, P. Stattin, M. Johansson, J.M. Chan, P. Gann, S.E. Oliver, J.M. Holly, J. Donovan, F. Meyer, I. Bairati.

    • Administrative, technical, or logistic support: A. Fitzpatrick, G. Severi.

    • Collection and assembly of data: A.W. Roddam, P. Appleby, H.B. Carter, C. Chen, N.S. Weiss, S. Rinaldi, R. Kaaks, J.A.M.J.L. Janssen, M.F. Wildhagen, E.A. Platz, E. Giovannucci, C. Schaefer, C.P. Quesenberry, J.H. Vogelman, G.G. Giles, P. Stattin, M. Johansson, J.M. Chan, P. Gann, S.E. Oliver, J.M. Holly, F. Meyer, I. Bairati.

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    1. Ann Intern Med October 7, 2008 vol. 149 no. 7 461-471
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