The IGF system in prostate cancer aetiology: a systematic review and meta-analysis


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Mari-Anne Rowlands1, David Gunnell1, Ross Harris1, Lars Vatten2, Jeff Holly1, Richard Martin1

1University of Bristol, Bristol, UK, 2Norwegian University of Science and Technology, Trondheim, Norway

Abstract

Background

Insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. We systematically reviewed studies reporting associations of circulating IGFs and IGFBPs with prostate cancer.

Method

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.

Results

The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) for IGF-I; 10 (923) for IGF-II; 3 (485) for IGFBP-1; 5 (577) for IGFBP-2; 29 (6,541) for IGFBP-3; and 11 (3,545) for the IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in exposure, 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 I² > 75%), partly explained by study design: the magnitude of associations was smaller in prospective versus retrospective studies. Associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease.

Conclusion

Our meta-analysis, which included three to five-times as many IGF-I studies as previous meta-analyses, confirms that raised circulating lGF-I is consistently associated with prostate cancer risk. There was an inverse association between IGFBP-3 and prostate cancer, but little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer aetiology.

Background

Insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. We systematically reviewed studies reporting associations of circulating IGFs and IGFBPs with prostate cancer.

Method

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.

Results

The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) for IGF-I; 10 (923) for IGF-II; 3 (485) for IGFBP-1; 5 (577) for IGFBP-2; 29 (6,541) for IGFBP-3; and 11 (3,545) for the IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in exposure, 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 I² > 75%), partly explained by study design: the magnitude of associations was smaller in prospective versus retrospective studies. Associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease.

Conclusion

Our meta-analysis, which included three to five-times as many IGF-I studies as previous meta-analyses, confirms that raised circulating lGF-I is consistently associated with prostate cancer risk. There was an inverse association between IGFBP-3 and prostate cancer, but little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer aetiology.