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Publication - Dr Claire Perks

    Reassessing the association between circulating Vitamin D and IGFBP-3

    observational and Mendelian randomization estimates from independent sources

    Citation

    Tan, V, Biernacka, K, Dudding, T, Bonilla, C, Gilbert, B, Kaplan, RC, Qi, Q, Teumer, A, Martin, R, Perks, C, , Timpson, N & Holly, JMP, 2018, ‘Reassessing the association between circulating Vitamin D and IGFBP-3: observational and Mendelian randomization estimates from independent sources’. Cancer Epidemiology, Biomarkers and Prevention.

    Abstract

    Background:
    Circulating insulin-like growth factor binding protein 3 (IGFBP-3) has been associated with PCa. Preclinical studies found that vitamin D regulates IGFBP-3 expression, although evidence from epidemiological studies are conflicting.

    Methods:
    Mendelian Randomisation analyses (MR) were conducted to reassess associations between IGFBP-3 and Prostate cancer (PCa) risk and advanced PCa using summary statistics from the PRACTICAL consortium (44,825cases;27,904controls). Observational and MR analyses were conducted to assess the relationship between inactive vitamin D (25(OH)D) and IGFBP-3 using data from the ProtecT study (1,366cases;1,071controls) and summary statistics from the CHARGE consortium (n=18,995).

    Results:
    The odds ratio (OR) for PCa per standard deviation (SD) unit increase in circulating IGFBP-3 was 1.14(95%CI:1.02-1.28). The OR for advanced PCa per SD unit increase in IGFBP-3 was 1.22(95%CI:1.07-1.40). Observationally, a SD increase in 25(OH)D was associated with a 0.1SD(95%CI:0.05, 0.14) increase in IGFBP-3. MR analyses found little evidence for a causal relationship between circulating 25(OH)D and IGFBP-3 in the circulation.

    Conclusions:
    This study provided confirmatory evidence that IGFBP-3 is a risk factor for PCa risk and progression. Observationally, there was evidence that 25(OH)D is associated with IGFBP-3, but MR analyses suggested that these findings were unlikely to be causal. Findings may be limited by the nature of instrumentation of 25(OH)D and IGFBP-3 and the utility of circulating measures. 25(OH)D appears unlikely to be causally related to IGFBP-3 in the circulation, however, our findings do not preclude causal associations at the tissue level.

    Impact:
    IGFBP-3 is a PCa risk factor but 25(OH)D are unlikely to be causally related to IGFBP-3 in the circulation.

    Full details in the University publications repository