Cancer Causes & Control

, Volume 11, Issue 8, pp 765–771 | Cite as

Endogenous risk factors for childhood leukemia in relation to the IGF system (Greece)

  • Eleni Petridou
  • Alkistis Skalkidou
  • Nick Dessypris
  • Maria Moustaki
  • Christos Mantzoros
  • Evangelos Spanos
  • Dimitrios Trichopoulos


Objective: Insulin-like growth factor-1 (IGF-1) and its principal binding protein-3 (IGFBP-3) are central in the mediation of the effect of growth hormone, and the IGF system has been reported to play a role in the pathogenesis of childhood leukemia.

Methods: To further evaluate the hypothesis connecting the IGF system to this disease, we have examined whether IGF-1 and IGFBP-3 are associated with the two main endogenous risk factors for childhood leukemia, namely gender and birth weight, since boys and heavier newborns are known to be at higher risk. IGF-1 and IGFBP-3 were measured under code in the serum of 118 apparently healthy children aged 0–14years and the values of each of these components were regressed on age, gender and birth weight. Insulin-like growth factor-2 (IGF-2), as a dependent variable, and anemia during the corresponding pregnancy, as a predictor variable, were also evaluated for exploratory purposes.

Results: In the total data set, IGF-1 was positively associated with birth weight (p = 0.0001), whereas girls had higher levels of IGFBP-3 (p = 0.01).

Conclusions: It appears that the associations of measured components of the IGF system with the examined risk factors for childhood leukemia are largely compatible with those that would have been expected, if this system played a role in the pathogenesis of childhood leukemia.

birth weight childhood leukemia gender insulin-like growth factor IGF 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami H-O (1997) Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76: 1115–1118.Google Scholar
  2. 2.
    Chan JM, Stampfer MJ, Giovannucci E, et al. (1998) Circulating insulin-like growth factor-1 and prostate cancer risks: a prospective study. Science 279: 563–566.Google Scholar
  3. 3.
    Wolk A, Mantzoros CS, Andersson SO, et al. (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 90: 911–915.Google Scholar
  4. 4.
    Peyrat JP, Bonneterre J, Hecquet B, et al. (1993) Plasma insulin-like growth factor-I (IGF-I) concentrations in human breast cancer. Eur J Cancer 29A: 492–497.Google Scholar
  5. 5.
    Bruning PF, Van Doorn J, Bonfrer JM, et al. (1995) Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer 62: 266–270.Google Scholar
  6. 6.
    Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS (1998) Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology 9: 570–573.Google Scholar
  7. 7.
    Hankinson SE, Willett WC, Conditz GA, et al. (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351: 1393–1396.Google Scholar
  8. 8.
    Kawamoto K, Onodera H, Kondo S, et al. (1998) Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. Oncology 55: 242–248.Google Scholar
  9. 9.
    Ma J, Pollak MN, Giovannucci E, et al. (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91: 620–625.Google Scholar
  10. 10.
    Manousos O, Souglakos J, Bosetti C, et al. (1999) IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 83: 15–17.Google Scholar
  11. 11.
    Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X (1999) Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Natl Cancer Inst 91: 151–156.Google Scholar
  12. 12.
    Rosen CJ, Conover C (1997) Growth hormone/insulin-like growth factor-1 axis in aging: a summary of a National Institutes of Aging-sponsored symposium. J Clin Endocrinol Metab 82: 3919–3922.Google Scholar
  13. 13.
    Petridou E, Dessypris N, Spanos E, et al. (1999) Insulin-like growth factor-1 and binding protein-3 in relation to childhood leukaemia. Int J Cancer 80: 494–496.Google Scholar
  14. 14.
    Ritzen EM (1993) Does growth hormone increase the risk of malignancies? Hormones Res 39: 99–101.Google Scholar
  15. 15.
    MacMahon B, Newill VA (1962) Birth characteristics of children dying of malignant neoplasms. J Natl Cancer Inst 28: 231–244.Google Scholar
  16. 16.
    Robison LL, Codd M, Gunderson P, Neglia JP, Smithson WA, King FLL (1987) Birth weight as a risk factor for childhood acute lymphoblastic leukaemia. Pediatr Hematol Oncol 4: 63–72.Google Scholar
  17. 17.
    Zack M, Adami H-O, Ericson A (1991) Maternal and perinatal risk factors for childhood leukaemia. Cancer Res 51: 3696–3701.Google Scholar
  18. 18.
    Broomhall J, May R, Lilleyman JS, Milner RDG (1983) Height and lymphoblastic leukaemia. Arch Dis Child 58: 300–301.Google Scholar
  19. 19.
    Ross JA, Perentesis JP, Robison LL, Davies SM (1996) Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7: 553–559.Google Scholar
  20. 20.
    Petridou E, Trichopoulos D, Kalapothaki V, et al. (1997) The risk profile of childhood leukaemia in Greece: a nationwide case-control study. Br J Cancer 76: 1241–1247.Google Scholar
  21. 21.
    Reiter EO, Rosenfeld RG (1999) Normal and aberrant growth. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology, 9th edn. Philadelphia: WB Saunders, pp. 1440.Google Scholar
  22. 22.
    Gurney JG, Severson RK, Davis S, Robison LL (1995) Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type. Cancer 75: 2186–2195.Google Scholar
  23. 23.
    Linet MS, Cartwright RA (1996) The leukemias. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention, 2nd edn. New York: Oxford University Press, pp. 841–892.Google Scholar
  24. 24.
    McNally RJ, Rowland D, Roman E, Cartwright RA (1997) Age and sex distributions of hematological malignancies in the UK. Hematol Oncol 15: 173–189.Google Scholar
  25. 25.
    Jackson N, Menon BS, Zarina W, Zawawi N, Naing NN (1999) Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes. Ann Hematol 78: 233–236.Google Scholar
  26. 26.
    Fasal E, Jackson EW, Kauber MR (1971) Birth characteristics and leukemia in childhood. J Natl Cancer Inst 47: 501–509.Google Scholar
  27. 27.
    Hirayama T (1980) Descriptive and analytical epidemiology of childhood malignancy in Japan. In: Kobayashi N, ed. Recent Advances in Management of Children with Cancer. Tokyo: Children's Cancer Association of Japan, pp. 27–43.Google Scholar
  28. 28.
    Daling JR, Starzyk P, Olshan AF, Weiss NS (1984) Birth weight and the incidence of childhood cancer. J Natl Cancer Inst 72: 1039–1041.Google Scholar
  29. 29.
    Chow W-H, Linet MS, Li. JM, Greenberg RS (1996) Cancers in children. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention, 2nd edn. New York: Oxford University Press, pp. 1331–1369.Google Scholar
  30. 30.
    Gluckman PD, Johnson-Barrett JJ, Butler JH, Edgar BW, Gunn TR (1983) Studies of insulin-like growth factors-I and-II by specific radioligand assays in umbilical cord blood. Clin Endocrinol 19: 405–413.Google Scholar
  31. 31.
    Lasarre C, Hardouin S, Daffos F, Forestier F, Frankenne F, Binoux M(1991) Serum insulin-like growth factors and insulin-like growth factor binding proteins in the human fetus. Relationships with growth in normal subjects with intrauterine growth retardation. Ped Res 29: 219–225.Google Scholar
  32. 32.
    Simmons D (1995) Interrelation between umbilical cord serum sex hormones, sex hormone-binding globulin, insulin-like growth factor 1, and insulin in neonates from normal pregnancies and pregnancies complicated by diabetes. J Clin Endocrinol Metab 80: 2217–2221.Google Scholar
  33. 33.
    Estrov Z, Meir R, Barak Y, Zaizov R, Zadik Z (1991) Human growth hormone and IGF-1 enhances the proliferation of leukemic blasts. J Clin Oncol 9: 394–399.Google Scholar
  34. 34.
    Sanders M, Sorba S, Daniak N (1993) Insulin-like growth factors stimulate erythropoiesis in serum-substituted umbilical cord blood cultures. Exp Hematol 21: 25–30.Google Scholar

Copyright information

© Klucwer Academic Publishers 2000

Authors and Affiliations

  • Eleni Petridou
    • 1
    • 2
  • Alkistis Skalkidou
    • 3
  • Nick Dessypris
    • 3
  • Maria Moustaki
    • 3
  • Christos Mantzoros
    • 4
  • Evangelos Spanos
    • 5
  • Dimitrios Trichopoulos
    • 3
    • 2
  1. 1.Department of Hygiene and EpidemiologyAthens University Medical SchoolAthensGreece
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Department of Hygiene and EpidemiologyAthens University Medical SchoolAthensGreece
  4. 4.Division of EndocrinologyBeth Israel Deaconess Medical CentreBostonUSA
  5. 5.BiomedInternational Diagnostic CentreAthensGreece

Personalised recommendations