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Meta-Analysis
. 2009 May 15;124(10):2416-29.
doi: 10.1002/ijc.24202.

Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis

Mari-Anne Rowlands  1 , David Gunnell, Ross Harris, Lars J Vatten, Jeff M P Holly, Richard M Martin
Affiliations
Meta-Analysis

Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis

Mari-Anne Rowlands et al. Int J Cancer. .

Abstract

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-1: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 = 1.18 (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 lGF-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-1 or IGFBP-2 in prostate cancer risk.

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Figures

Figure 1
Figure 1
Flow diagram showing the number of studies included in and excluded from the meta-analysis
Figure 2
Figure 2
Funnel plots of standard errors (SE) of the log odds ratio (OR) of prostate cancer (Y axis) versus the log OR of prostate cancer (X axis) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. The vertical line is drawn at the pooled log OR. Diagonal lines indicate the pseudo 95% confidence interval.
Figure 3
Figure 3
Forest plot of the association of IGF-I with prostate cancer showing the effect of a one standard deviation increase in IGF-I. Squares indicate the study-specific effect estimate, with the size proportional to the inverse of the variance, with horizontal lines showing 95% confidence intervals. The dashed vertical line and diamonds (95% confidence interval) are the pooled estimates based on random or fixed effects meta-analysis models.
Figure 4
Figure 4
Forest plot of the association of IGF-II with prostate cancer showing the effect of a one standard deviation increase in IGF-II. Squares indicate the study-specific effect estimate, with the size proportional to the inverse of the variance, with horizontal lines showing 95% confidence intervals. The dashed vertical line and diamonds (95% confidence interval) are the pooled estimates based on random or fixed effects meta-analysis models.
Figure 5
Figure 5
Forest plot of the association of IGFBP-3 with prostate cancer showing the effect of a one standard deviation increase in IGFBP-3. Squares indicate the study-specific effect estimate, with the size proportional to the inverse of the variance, with horizontal lines showing 95% confidence intervals. The dashed vertical line and diamonds (95% confidence interval) are the pooled estimates based on random or fixed effects meta-analysis models.
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