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Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study

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Abstract

Purpose

Active monitoring of prostate cancer requires the selection of low-risk cancers and subsequent identification of disease progression. Our objective was to determine whether serum insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2 or IGFBP-3 at diagnosis (potential biomarkers of prognosis), and repeated measures of IGFBP-2 (potential biomarker of tumour growth), were associated with annual change in PSA and PSA doubling time (PSADT), proxies for disease progression.

Methods

We investigated associations of circulating IGFs and IGFBPs with PSA measures using multilevel models, in 909 men (recruited between 1999 and 2009) with PSA-detected clinically localized prostate cancer undergoing active monitoring in the United Kingdom. Each man had an average of 14 measurements of PSA during a mean of 4-year follow-up.

Results

IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were not associated with baseline PSA. There was weak evidence that IGF-I at diagnosis was positively associated with a rapid post-diagnosis PSADT (≤4 years vs. >4 years): OR 1.34 (95 % CI 0.98, 1.81) per SD increase in IGF-I. IGFBP-2 increased by 2.1 % (95 % CI 1.4, 2.8) per year between 50 and 70 years, with no association between serial IGFBP-2 levels and PSADT. There was no evidence that serum IGF-II, IGFBP-2, or IGFBP-3, or post-diagnosis IGFBP-2, were associated with PSA kinetics in men with PSA-detected localized prostate cancer.

Conclusions

The weak association of IGF-I with PSADT requires replication in larger datasets, and more definitive evidence will be provided on the maturity of long-term active monitoring cohorts with relevant clinical outcomes (metastasis and prostate cancer mortality).

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Acknowledgments

The authors would like to acknowledge the tremendous contribution of all members of the ProtecT study research group, and especially the following who were involved in this research: Prasad Bollina, Sue Bonnington, Lynne Bradshaw, James Catto, Debbie Cooper, Michael Davis, Liz Down, Andrew Doble, Alan Doherty, Garrett Durkan, Emma Elliott, David Gillatt, Pippa Herbert, Peter Holding, Joanne Howson, Mandy Jones, Roger Kockelbergh, Howard Kynaston, Athene Lane, Teresa Lennon, Norma Lyons, Hing Leung, Malcolm Mason, Hilary Moody, Philip Powell, Alan Paul, Stephen Prescott, Derek Rosario, Patricia O’Sullivan, Pauline Thompson, Lynne Bradshaw, Sarah Tidball. They would also like to thank the men who participated in this study and the NIHR Cambridge Biomedical Research Centre. Val Laundy, Semih Dogan, Li Zeng, Ola Wojtowicz, and Kalina Zdunek performed the IGF assays. This work was supported by Cancer Research UK project grant C18281/A7062. The ProtecT study is funded by the UK Health Technology Assessment (HTA) Programme of the National Institute for Health Research, HTA 96/20/99; ISRCTN20141297. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. The authors would like to acknowledge the support of the National Cancer Research Institute (NCRI) formed by the Department of Health, the Medical Research Council (MRC), and Cancer Research UK. The NCRI provided funding through ProMPT (Prostate Mechanisms of Progression and Treatment), and this support is gratefully acknowledged. RMM is affiliated to the CAITE centre, which is supported by the MRC (G0600705) and the University of Bristol. DG, FH, JD, and DN are NIHR Senior Investigators. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK

    Mari-Anne Rowlands, Kate Tilling, Chris Metcalfe, David Gunnell, Athene Lane, Michael Davis, Jenny Donovan & Richard M. Martin

  2. School of Clinical Sciences North Bristol, University of Bristol, Bristol, BS10 5NB, UK

    Jeff M. P. Holly

  3. Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Freddie Hamdy

  4. Department of Oncology, University of Cambridge, Box 279 (S4), Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK

    David E. Neal

  5. MRC Centre for Causal Analysis in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK

    Richard M. Martin

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  1. Mari-Anne Rowlands
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  2. Kate Tilling
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  3. Jeff M. P. Holly
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  4. Chris Metcalfe
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  10. David E. Neal
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  11. Richard M. Martin
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Correspondence to Mari-Anne Rowlands.

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Rowlands, MA., Tilling, K., Holly, J.M.P. et al. Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study. Cancer Causes Control 24, 39–45 (2013). https://doi.org/10.1007/s10552-012-0087-7

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  • DOI: https://doi.org/10.1007/s10552-012-0087-7

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