Regular Article

BJC Open article

British Journal of Cancer (2001) 85, 1695–1699. doi:10.1054/bjoc.2001.2172
Published online 27 November 2001

IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai

N M Probst-Hensch1, J-M Yuan3, F Z Stanczyk3, Y-T Gao4, R K Ross2 and M C Yu2

  1. 1Institute of Social and Preventive Medicine, University of Basel, Steinengraben 49, Basel, 4051, Switzerland
  2. 2USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
  3. 3Dept. of OB/GYN, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
  4. 4Shanghai Cancer Institute, Shanghai, 200032, Peoples’ Republic of China

Received 12 June 2001; Revised 5 September 2001; Accepted 10 September 2001; Corrected online 16 November 2011



This is the first study to investigate the associations of IGF-1, IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospectively collected blood samples from an Oriental population. Between 1986 and 1989 serum samples were collected at baseline from 18244 men, aged 45–65 years, without a history of cancer and living in Shanghai, China. IGF-1, IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort, who were matched to the index cases by neighbourhood of residence, age, and year and month of sample collection. Serum IGF-1 was not associated with risk of colorectal cancer. IGF-2 and IGFBP-3, on the other hand, exhibited statistically significant, positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment (within 8 years). After adjustment for body mass index, cigarette smoking and alcohol intake, men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 (95% Cl = 1.67–4.50; 2-sided P for trend = 0.0008) and 2.85 (95% Cl = 1.69–4.81; 2-sided P for trend = 0.01), respectively. Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer. © 2001 Cancer Research Campaign


IGF-1; IGF-2; IGFBP-3; colorectal cancer



  1. Cadoret A, Baron-Delage S, Bertrand F, Kornprost M, Groyer A, Gespach C, Capeau J and Cherqui G (1998) Oncogene-induced up- regulation of Caco-2-cell proliferation involves IGF-II gene activation through a protein kinase C-mediated pathway. Oncogene 17: 877–887 | Article |
  2. Cui H, Horon I, Ohlsson R, Hamilton SR and Feinberg AP (1998) Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nature Med 4: 1276–1280
  3. Di Popolo AD, Memoli A, Apicella A, Tuccillo C, Palma A, Ricchi P, Acquaviva AM and Zarrilli R (2000) IGF-II/IGF-I receptor pathway up-regulates COX-2 mRNA expression and PGE2 synthesis in Caco-2 human colon carcinoma cells. Oncogene 19: 5517–5524 | Article | PubMed | ISI | ChemPort |
  4. EI-Atiq F, Garrouste F, Remacle-Bonnet M, Sastre B and Pommier G (1994) Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. Int J Cancer 57: 491–497
  5. Ferry RJ, Cerri RW and Cohen P (1999) Insulin-like growth factor binding proteins: new proteins. new functions. Horm Res 51: 53–67 | Article | PubMed | ISI | ChemPort |
  6. Freier S, Weiss O, Eran M, Flyvbjerg A, Dahan R, Nephesh I, Safra T, Shiloni E and Raz I (1999) Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon. Gut 44: 704–708 | PubMed | ISI | ChemPort |
  7. Giovannucci E (1999) Insulin-like growth factor-1 and binding protein-3 and risk of cancer. Horm Res 51, (Suppl 3) 34–41 | Article | PubMed | ISI | ChemPort |
  8. Giovannucci E, Pollak MN, Platz EA, Willett WC and Stampfer MJ et al (2000) A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomark Prev 9: 345–349 | ISI | ChemPort |
  9. Hassan AB and Howell JA (2000) Insulin-like growth factor II supply modifies growth of intestinal adenoma in Apc(Min/+) mice. Cancer Res 60: 1070–1076 | PubMed | ISI | ChemPort |
  10. Hosmer DW and Lemeshow S (1989) Applied Logistic Regression. John Wiley & Sons: New York
  11. Jones JI and Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews 16: 3–34
  12. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE and Riboli E (2000) Serum C-peptide insulin-like growth factor-I (IGF-I). IGF-binding proteins and colorectal cancer risk in women. J Natl Cancer Inst 92: 1592–1600 | Article | PubMed | ChemPort |
  13. Kansra S, Ewton DZ, Wang J and Friedman E (2000) IGFBP-3 mediates TGF beta 1 response in colon cancer cells. Int J Cancer 87: 373–378 | Article | PubMed | ISI | ChemPort |
  14. Lamonerie T, Lavialle C, Haddada H and Brison O (1995a) IGF- 2 autocrine stimulation in tumorigenic clones of a human colon-carcinoma cell line. Int J Cancer 61: 587–592 | PubMed |
  15. Lamonerie T, Lavialle C, de Galle B, Binoux M and Brison O (1995b) Constitutive or inducible overexpression of the IGF-2 gene in cells of a human colon carcinoma cell line. Exp Cell Res 216: 342–351
  16. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH and Stampfer MJ (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-1 and IGF-binding protein-3. J Nati Cancer Inst 91: 620–625
  17. Manousos O, Souglakos J, Bosetti C, Tzonou A, Chatzidakis V, Trichopoulos D, Adami H-O and Mantzoros C (1999) IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 83: 15–17
  18. Renehan AG, Painter JE, O'Halloran D, Atkin WS, Potten CS, O'Dwyer ST and Shalet SM (2000) Circulating insulin-like growth factor II and colorectal adenomas. J Clin Endocrinol Metab 85: 3402–3408 | Article | ISI | ChemPort |
  19. Szepeshazi K, Schally AV, Groot K, Armatis P, Halmos G, Herbert F, Szende B, Varga JL and Zarandi M (2000) Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. Br J Cancer 82: 1724–1731 | Article | PubMed | ChemPort |
  20. Thissen JP, Ketelslegers JM and Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocrine Reviews 15: 80–101
  21. Yuan JM, Ross RK, Wang XL, Gao Y-T, Henderson BE and Yu MC (1996) Morbidity and mortality in relation to cigarette smoking in Shanghai. China. JAMA 275: 1646–1650
  22. Zou T, Fleisher A, Kong D, Yin J, Souza R, Wang S and Smolinski KN (1998) Abraham JM, Meltzer SJ. Sequence alterations of IGFBP3 in neoplastic and normal gastrointestinal tissues. Cancer Res 58: 4802–4804
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