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Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer

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Abstract

Context

Many studies have reported associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer development, but none have investigated their association with fatal progression of prostate cancer.

Objective

We investigated associations of circulating IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with all-cause and prostate cancer mortality in men with clinically identified prostate cancer, stratified by whether localised (stage T1 or T2) or advanced (T3, T4, N1 or M1) at diagnosis.

Design, setting and participants

UK hospital-based cohort study of 396 men with prostate cancer, diagnosed between 1990 and 2008, with mean follow-up of 3.7 years.

Main outcome measures

All-cause and prostate cancer–specific mortality.

Results

In men with advanced cancer, there was some evidence that IGF-I was positively associated (HR 1.20; 95% CI: 0.96, 1.49; p = 0.11) and IGFBP-3 was inversely associated (HR 0.84; 95% CI: 0.70, 1.01; p = 0.07) with all-cause mortality after controlling for age, treatment status, smoking, prostate-specific antigen and Gleason grade at diagnosis. There was some evidence that IGF-I was positively associated with prostate cancer mortality in advanced cases (HR 1.23; 95% CI: 0.94, 1.62; p = 0.13). In advanced cancers, associations of IGF-I with all-cause (HR 1.68; 95% CI: 1.28, 2.23; p < 0.001) and prostate cancer–specific (HR 1.59; 95% CI: 1.11, 2.28; p = 0.01) mortality strengthened (and were conventionally statistically significant) after further controlling for IGFBP-3.

Conclusions

Measures of IGF-I and IGFBP-3 may have potential as prognostic markers in predicting risk of death in men with advanced prostate cancer. Large, prospective studies with repeat IGFs and IGFBPs are now required.

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References

  1. Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37:4–66

    Article  Google Scholar 

  2. Johansson JE, Holmberg L, Johansson S, Bergstrom R, Adami HO (1997) Fifteen-year survival in prostate cancer. A prospective, population-based study in Sweden. JAMA 277:467–471

    Article  PubMed  CAS  Google Scholar 

  3. Concato J, Jain D, Uchio E, Risch H, Li WW, Wells CK (2009) Molecular markers and death from prostate cancer. Ann Intern Med 150:595–603

    PubMed  Google Scholar 

  4. Fall K, Garmo H, Andren O, Bill-Axelson A, Adolfsson J, Adami HO, Johansson JE, Holmberg L (2007) Prostate-specific antigen levels as a predictor of lethal prostate cancer. JNCI J Natl Cancer Inst 99:526–532

    Article  Google Scholar 

  5. Metcalfe C, Tilling K, Davis M, Lane JA, Martin RM, Kynaston H, Powell P, Neal DE, Hamdy F, Donovan JL (2009) Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study. Br J Cancer 101:390–394

    Article  PubMed  CAS  Google Scholar 

  6. Pollak M (2008) Insulin, insulin-like growth factors and neoplasia. Best Pract Res Clin Endocrinol Metab 22:625–638

    Article  PubMed  CAS  Google Scholar 

  7. Rowlands M, Gunnell D, Harris R, Vatten LJ, Holly JMP, Martin RM (2009) Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer 124:2416–2429

    Article  PubMed  CAS  Google Scholar 

  8. Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, Hsing AW, Lacey JV Jr, Helzlsouer K, Rinaldi S, Riboli E, Kaaks R, Janssen JAMJ, Wildhagen MF, Schroder FH, Platz EA, Pollak M, Giovannucci E, Schaefer C, Quesenberry CP Jr, Vogelman JH, Severi G, English DR, Giles GG, Stattin P, Hallmans G, Johansson M, Chan JM, Gann P, Oliver SE, Holly JM, Donovan J, Meyer F, Bairati I, Galan P (2008) Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med 149:461–471

    PubMed  Google Scholar 

  9. Petridou E, Salkidou A, Dessypris N, Moustaki M, Mantzoros C, Spanos E, Trichopoulos D (2001) Insulin-like growth factor binding protein-3 predicts survival from acute childhood leukemia. Oncology 60:252–257

    Article  PubMed  CAS  Google Scholar 

  10. Rocha RL, Hilsenbeck SG, Jackson JG, VanDenBerg CL, Weng C, Lee AV, Yee D (1997) Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin Cancer Res 3:103–109

    PubMed  CAS  Google Scholar 

  11. Wakai K, Ito Y, Suzuki K, Tamakoshi A, Seki N, Ando M, Ozasa K, Watanabe Y, Kondo T, Nishino Y, Ohno Y (2002) Serum insulin-like growth factors, insulin-like growth factor-binding protein-3, and risk of lung cancer death: a case-control study nested in the Japan Collaborative Cohort (JACC) Study. Jpn J Cancer Res 93:1279–1286

    Article  PubMed  CAS  Google Scholar 

  12. Yu H, Levesque MA, Khosravi MJ, Papanastasiou-Diamandi A, Clark GM, Diamandis EP (1998) Insulin-like growth factor binding protein-3 and breast cancer survival. Int J Cancer 79:624–628

    Article  PubMed  CAS  Google Scholar 

  13. Parker AS, Cheville JC, Lohse C, Cerhan JR, Blute ML (2003) Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. J Urol 170:420–424

    Article  PubMed  CAS  Google Scholar 

  14. Lin Y, Tamakoshi A, Kikuchi S, Yagyu K, Obata Y, Ishibashi T, Kawamura T, Inaba Y, Kurosawa M, Motohashi Y, Ohno Y (2004) Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, and the risk of pancreatic cancer death. Int J Cancer 110:584–588

    Article  PubMed  CAS  Google Scholar 

  15. Vadgama JV, Wu Y, Datta G, Khan H, Chillar R (1999) Plasma insulin-like growth factor-I and serum IGF-binding protein 3 can be associated with the progression of breast cancer, and predict the risk of recurrence and the probability of survival in African-American and Hispanic women. Oncology 57:330–340

    Article  PubMed  CAS  Google Scholar 

  16. Greene FL, Page DL (2002) Genitourinary sites. Prostate. In: Green FL, Page DL, Fleming ID, Fritz AD, Balch CM, Haller DG, Morrow M (eds) AJCC cancer staging manual. Springer, New York, pp 309–317

  17. Juul A, Main K, Blum WF, Lindholm J, Ranke MB, Skakkebaek NE (1994) The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol 41:85–93

    Article  CAS  Google Scholar 

  18. Holly J, Perks C (2006) The role of insulin-like growth factor binding proteins. Neuroendocrinology 83:154–160

    Article  PubMed  CAS  Google Scholar 

  19. Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277:38205–38211

    Article  PubMed  CAS  Google Scholar 

  20. Playford MP, Bicknell D, Bodmer WF, Macaulay VM (2000) Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of B-catenin. Proc Natl Acad Sci USA 97:12103–12108

    Article  PubMed  CAS  Google Scholar 

  21. Jones JI, Clemmons D (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34

    PubMed  CAS  Google Scholar 

  22. Satariano WA, Ragland KE, Van Den Eeden SK (1998) Cause of death in men diagnosed with prostate carcinoma. Cancer 83:1180–1188

    Article  PubMed  CAS  Google Scholar 

  23. Friedrich N, Haring R, Nauck M, Ludemann J, Rosskopf D, Spilcke-Liss E, Felix SB, Dorr M, Brabant G, Volzke H, Wallaschofski H (2009) Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab 94:1732–1739

    Article  PubMed  CAS  Google Scholar 

  24. Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489

    Article  PubMed  CAS  Google Scholar 

  25. Lawlor DA, Ebrahim S, Smith GD, Cherry L, Watt P, Sattar N (2008) The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: findings from the prospective British Women’s Heart and Health Study. Atherosclerosis 201:198–204

    Article  PubMed  CAS  Google Scholar 

  26. Goodman-Gruen D, Barrett-Connor E (1997) Epidemiology of insulin-like growth factor-I in elderly men and women: the rancho bernardo study. Am J Epidemiol 145:970–976

    PubMed  CAS  Google Scholar 

  27. Botker HE, Skjaerbaek C, Eriksen UK, Schmitz O, Orksov H (1997) Insulin-like growth factor-I, insulin, and angina pectoris secondary to coronary atherosclerosis, vasospasm, and syndrome X. Am J Cardiol 79:961–963

    Article  PubMed  CAS  Google Scholar 

  28. Sandhu MS (2005) Insulin-like growth factor-l and risk of type 2 diabetes and coronary heart disease: molecular epidemiology. Endocr Dev 9:44–54

    Article  PubMed  CAS  Google Scholar 

  29. Rowlands M-A, Holly J, Gunnell D, Gilbert R, Donovan J, Lane J, Marsden G, Collin S, Hamdy F, Neal D, Martin R (2010) The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for cancer and Treatment) study. Cancer Causes Control 21:1842

    Article  Google Scholar 

  30. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279:563–566

    Article  PubMed  CAS  Google Scholar 

  31. Platz EA, Pollak MN, Leitzmann MF, Stampfer MJ, Willett WC, Giovannucci E (2005) Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era. Cancer Causes Control 16:255–262

    Article  PubMed  Google Scholar 

  32. Thissen J-P, Ketelslegers J-M, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocr Rev 15:80–101

    PubMed  CAS  Google Scholar 

  33. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the following who were involved in this research: Laura Proctor, Leila Ayandi, Ewa Dudziec, Pete Holding, Claire Ward, Irene Sharkey, Michael Slater, Sue Kilner, Joanne Howson and Rajeev Kumar. They also thank the men who participated in this study. 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 authors 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 works within 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.

Author information

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, David Gunnell, 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 & Gemma Marsden

  4. Academic Urology Unit, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S10 2RX, UK

    Joshua Phillips & Louise Goodwin

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

    David E. Neal

  6. 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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Correspondence to Richard M. Martin.

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Rowlands, MA., Holly, J.M.P., Hamdy, F. et al. Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer. Cancer Causes Control 23, 347–354 (2012). https://doi.org/10.1007/s10552-011-9883-8

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  • DOI: https://doi.org/10.1007/s10552-011-9883-8

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