• Andrew W Roddam, Naomi E Allen, Paul Appleby, Timothy J Key, Luigi Ferrucci, CarterH BallentineHB, E Jeffrey Metter, Chu Chen, Noel S Weiss, Annette Fitzpatrick, Ann W Hsing, James V Lacey, Kathy Helzlsouer, Sabina Rinaldi, Elio Riboli, Rudolf Kaaks, Joop A M J L Janssen, Mark F Wildhagen, Fritz H Schröder, Elizabeth A Platz, Michael Pollak, Edward Giovannucci, Catherine Schaefer, Charles P Quesenberry, Joseph H Vogelman, Gianluca Severi, Dallas R English, Graham G Giles, Pär Stattin, Göran Hallmans, Mattias Johansson, June M Chan, Peter Gann, Steven E Oliver, Jeff M Holly, Jenny Donovan, François Meyer, Isabelle Bairati, and Pilar Galan.
• Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. andrew.roddam@ceu.ox.ac.uk
• Ann. Intern. Med. 2008 Oct 7; 149 (7): 461-71, W83-8.

BackgroundSome, 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.PurposeTo assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.Data SourcesStudies identified in PubMed, Web of Science, and CancerLit.Study SelectionThe 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 ExtractionInvestigators 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 SynthesisThe 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.LimitationsInsulin-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.ConclusionHigh circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

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