Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 124, Issue 10, Pages 2416-2429Publisher
WILEY
DOI: 10.1002/ijc.24202
Keywords
prostate cancer; meta-analysis; insulin-like growth factor; insulin-like growth factor binding protein
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Funding
- Economic and Social Research Council [ES/G007543/1] Funding Source: researchfish
- Medical Research Council [G0500966] Funding Source: researchfish
- ESRC [ES/G007543/1] Funding Source: UKRI
- MRC [G0500966] Funding Source: UKRI
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Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3 and 11 (3,545) IGF-I:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.19 (0.90, 1.54); IGFBP-3,, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I-2 > 75%), partly explained by study design: the magnitude of associations was smaller in prospective vs. retrospective studies, and for IGFBP-3, the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating IGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-I or IGFBP-2 in prostate cancer risk. (C) 2008 Wiley-Liss, Inc.
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