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A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Travis RC 1 , Appleby PN 1 , Martin RM 2 , Holly JMP 3 , Albanes D 4 , Black A 4 Show all authors , Bueno-de-Mesquita HBA 5 , Chan JM 6 , Chen C 7 , Chirlaque MD 8 , Cook MB 4 , Deschasaux M 9 , Donovan JL 2 , Ferrucci L 10 , Galan P 9 , Giles GG 11 , Giovannucci EL 12 , Gunter MJ 13 , Habel LA 14 , Hamdy FC 15 , Helzlsouer KJ 16 , Hercberg S 9 , Hoover RN 4 , Janssen JAMJL 17 , Kaaks R 18 , Kubo T 19 , Le Marchand L 20 , Metter EJ 10 , Mikami K 21 , Morris JK 22 , Neal DE 23 , Neuhouser ML 7 , Ozasa K 24 , Palli D 25 , Platz EA 26 , Pollak M 27 , Price AJ 1 , Roobol MJ 28 , Schaefer C 14 , Schenk JM 29 , Severi G 11 , Stampfer MJ 12 , Stattin P 30 , Tamakoshi A 31 , Tangen CM 32 , Touvier M 9 , Wald NJ 23 , Weiss NS 33 , Ziegler RG 4 , Key TJ 1 , Allen NE 34

Affiliations 

  • 1 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 2 School of Social and Community Medicine, University of Bristol, Bristol, UK
  • 3 School of Clinical Science, Faculty of Medicine, University of Bristol, Bristol, UK
  • 4 Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA
  • 5 Dt. for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, and Dt. of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands, and Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, CA, USA
  • 7 Division of Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 8 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, and CIBER Epidemiología y Salud Pública, Spain
  • 9 Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team, Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, F-93017, Bobigny, France
  • 10 Intramural Research Program, National Institute on Aging, Baltimore, MD, USA
  • 11 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia
  • 12 Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
  • 13 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • 14 Division of Research, Kaiser Permanente, Northern California, Oakland, California, USA
  • 15 Nuffield Department of Surgery, University of Oxford, UK
  • 16 The Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA
  • 17 Erasmus MC, Dept Internal Medicine, Rotterdam, the Netherlands
  • 18 Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
  • 19 University of Occupational and Environmental Health, Kitakyushu, Japan
  • 20 University of Hawaii Cancer Center, Honolulu, HI, USA
  • 21 Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 22 Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK
  • 23 Department of Oncology, University of Cambridge, UK
  • 24 Radiation Effects Research Foundation, Hiroshima, Japan
  • 25 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
  • 26 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • 27 Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada
  • 28 Erasmus MC, Dept of Urology Rotterdam, the Netherlands
  • 29 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 30 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden
  • 31 Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • 32 SWOG Statistical Center, Fred Hutchinson Cancer Research Center, and Department of Biostatistics, University of Washington, Seattle, WA, USA
  • 33 Human Genetics Foundation, Torino, Italy
  • 34 Clinical Trials Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
Cancer Res, 2016 04 15;76(8):2288-2300.
PMID: 26921328 DOI: 10.1158/0008-5472.CAN-15-1551

Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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