title: A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk.
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.
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Appleby
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.|Medical Research Council/University of Bristol Integrative Epidemiology Unit, University of Bristol, and National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: School of Clinical Science, Faculty of Medicine, University of Bristol, Bristol, UK.
authors.forename: Jeff M P
authors.initials: JMP
authors.lastname: Holly
authors.affiliation: Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: 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.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: H B As
authors.initials: HBA
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, CA, USA.
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: Division of Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, and CIBER Epidemiología y Salud Pública, Spain.
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
authors.affiliation: 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.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Deschasaux
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: 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.
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.affiliation: 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.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.|Department of Nutrition and Department of Medicine, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Division of Research, Kaiser Permanente, Northern California, Oakland, California, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.affiliation: Nuffield Department of Surgery, University of Oxford, UK.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: The Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA.
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.affiliation: 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.
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.affiliation: Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Erasmus MC, Dept Internal Medicine, Rotterdam, the Netherlands.
authors.forename: Joseph A M J L
authors.initials: JAMJL
authors.lastname: Janssen
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kubo
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.|Department of Neurology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.affiliation: Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mikami
authors.affiliation: Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK.
authors.forename: Joan K
authors.initials: JK
authors.lastname: Morris
authors.affiliation: Department of Oncology, University of Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Division of Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
authors.affiliation: Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ozasa
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.affiliation: Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Price
authors.affiliation: Erasmus MC, Dept of Urology Rotterdam, the Netherlands.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.affiliation: Division of Research, Kaiser Permanente, Northern California, Oakland, California, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Schenk
authors.affiliation: 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.|Human Genetics Foundation, Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tamakoshi
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, and Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.affiliation: 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.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Touvier
authors.affiliation: Department of Oncology, University of Cambridge, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wald
authors.affiliation: Human Genetics Foundation, Torino, Italy.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: Clinical Trials Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
mesh_terms: D000368:Aged; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D007334:Insulin-Like Growth Factor I