Journal
CANCER RESEARCH
Volume 76, Issue 8, Pages 2288-2300Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-15-1551
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Funding
- Cancer Research UK [19170, 16491] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10242] Funding Source: researchfish
- Cancer Research UK [A19169] Funding Source: Medline
- NCI NIH HHS [UG1 CA189974, R37 CA054281, U01 CA164973, P01 CA108964, R01 CA133891, P01 CA033619, UM1 CA182883, U10 CA037429, P01 CA055075] Funding Source: Medline
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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 (P-trend all <= 0.005), and IGFBP-1 was inversely associated weakly with risk (P-trend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (P-heterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, P-heterogeneity = 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. (C) 2016 AACR.
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