Objective: The insulin-like growth factor (IGF) system has been related to cell proliferation, obesity, diabetes, hyperinsulinemia and endometrial cancer risk. We used data from a case-control study conducted in Italy to provide additional information on the relation between the IGF system and endometrial cancer. Methods: A case-control study was conducted between 1999 and 2002 in Italy, including a total of 73 women with incident, histologically confirmed endometrial cancer and 108 controls admitted to the same hospital network for acute, nonneoplastic diseases. All subjects were interviewed using a validated questionnaire. Results: The odds ratios for endometrial cancer comparing the highest versus the lowest tertile of various IGF components were as follows: 0.5 [95% confidence interval (CI) 0.2–1.2] for free IGF-I, 1.1 (95% CI 0.5–2.6) for total IGF-I, 1.2 (95% CI 0.6–2.6) for total IGF-II, 2.4 (95% CI 1.0–5.9) for IGF binding protein (IGFBP)-1 and 0.8 (95% CI 0.4–2.0) for IGFBP-3. Further allowance for all IGF components in the model did not modify the results. The direct relation with IGFBP-1 was stronger and limited to heavier and older women. Conclusions: The present findings suggest a limited effect of the IGF system on endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with endometrial cancer risk in older women and in women with a higher body mass index.

Keywords:
Endometrial cancer, Insulin-like growth factor system, Obesity, Case-control study
1.
Parazzini F, La Vecchia C, Bocciolone L, Franceschi S: The epidemiology of endometrial cancer. Gynecol Oncol 1991;41:1–16.
2.
Parazzini F, La Vecchia C, Negri E, Riboldi GL, Surace M, Benzi G, Maina A, Chiaffarino F: Diabetes and endometrial cancer: An Italian case-control study. Int J Cancer 1999;81:539–542.
3.
Grady D, Ernster VL: Endometrial cancer; in Schottenfeld D, Fraumeni JF (eds): Cancer Epidemiology and Prevention. Oxford, Oxford University, 1996, pp 1058–1089.
4.
Kaaks R, Lukanova A, Kurzer MS: Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review. Cancer Epidemiol Biomarkers Prev 2002;11:1531–1543.
5.
Augustin LS, Gallus S, Bosetti C, Levi F, Negri E, Franceschi S, Dal Maso L, Jenkins DJ, Kendall CW, La Vecchia C: Glycemic index and glycemic load in endometrial cancer. Int J Cancer 2003;105:404–407.
6.
LeRoith D, Roberts CT Jr: The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127–137.
7.
Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, et al: Insulin-like growth factor I receptor primary structure: Comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 1986;5:2503–2512.
8.
Yee D, Lee AV: Crosstalk between the insulin-like growth factors and estrogens in breast cancer. J Mammary Gland Biol Neoplasia 2000;5:107–115.
9.
Li BD, Khosravi MJ, Berkel HJ, Diamandi A, Dayton MA, Smith M, Yu H: Free insulin-like growth factor-I and breast cancer risk. Int J Cancer 2001;91:736–739.
10.
Daughaday WH, Rotwein P: Insulin like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum and tissue concentrations. Endocr Rev 1989;10:68–91.
11.
Seppala M, Koistinen R, Rutanen E-M: Uterine endocrinology and paracrinology: Insulin-like growth factor binding protein-1 and placental protein 14 revisited. Hum Reprod 1994;9:917–925.
12.
Rutanen EM: Insulin-like growth factors in endometrial function. Gynecol Endocrinol 1998;12:399–406.
13.
Rutanen EM, Pekonen F, Makinen T: Soluble 34k binding protein inhibits the binding of insulin-like growth factor I to its cell receptors in human secretory phase endometrium: Evidence for autocrine/paracrine regulation of growth factor action. J Clin Endocrinol Metab 1988;66:173–180.
14.
Bermont L, Fauconnet S, Lamielle F, Adessi GL: Cell-associated insulin-like growth factor-binding proteins inhibit insulin-like growth factor-I-induced endometrial cancer cell proliferation. Cell Mol Biol 2000;46:1173–1182.
15.
Jones JI, D’Ercole AJ, Camacho-Hubner C, Clemmons DR: Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: Effects on affinity for IGF-I. Proc Natl Acad Sci USA 1991;88:7481–7485.
16.
Allen NE, Appleby PN, Kaaks R, Rinaldi S, Davey GK, Key TJ: Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Cancer Causes Control 2003;14:65–74.
17.
Cohen P: Serum insulin-like growth factor-I levels and prostate cancer risk – interpreting the evidence. J Natl Cancer Inst 1998;90:876–879.
18.
Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D: Insulin-like growth factor I and prostate cancer risk: A population-based, case-control study. J Natl Cancer Inst 1998;90:911–915.
19.
Pollak M, Beamer W, Zhang JC: Insulin-like growth factors and prostate cancer. Cancer Metastasis Rev 1998–1999;17:383–390.
20.
Signorello LB, Brismar K, Bergstrom R, Andersson S-O, Wolk A, Trichopoulos D, Adami HO: Insulin-like growth factor-binding protein-1 and prostate cancer. J Natl Cancer Inst 1999;91:1965–1967.
21.
Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL, Speizer FE: Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1998;90:1292–1299.
22.
Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ: 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 1999;91:620–625.
23.
Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X: Plasma levels of insulin-like growth factor-I and lung cancer risk: A case-control analysis. J Natl Cancer Inst 1999;91:151–156.
24.
Mathur SP, Mathur RS, Young RC: Cervical epidermal growth factor receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. Am J Reprod Immunol 2000;44:222–230.
25.
Petridou E, Dessypris N, Spanos E, Mantzoros C, Skalkidou A, Kalmanti M, Koliouskas D, Kosmidis H, Panagiotou JP, Piperopoulou F, Tzortzatou F, Trichopoulos D: Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia. Int J Cancer 1999;80:494–496.
26.
Ayabe T, Tsutsumi O, Sakai H, Yoshihawa H, Yano T, Kurimoto F, Taketani Y: Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-I in postmenopausal women with endometrial cancer. Endocr J 1997;44:419–424.
27.
Rutanen EM, Stenman S, Blum W, Karkkainen T, Lehtovirta P, Stenman UH: Relationship between carbohydrate metabolism and serum insulin-like growth factor system in post-menopausal women: Comparison of endometrial cancer patients with healthy controls. J Clin Endocrinol Metab 1993;77:199–204.
28.
Petridou E, Koukoulomatis P, Alexe DM, Voulgaris Z, Spanos E, Trichopoulos D: Endometrial cancer and the IGF system: A case-control study in Greece. Oncology 2003;64:341–345.
29.
Breslow NE, Day NE: Statistical Methods in Cancer Research. Lyon, International Agency for Research on Cancer, 1980, vol 1:The Analysis of Case-Control Studies, IARC Scientific Publication 32.
30.
Weiderpass E, Brismar K, Bellocco R, Vainio H, Kaaks R: Serum levels of insulin-like growth factor-1, IGF-binding protein 1 and 3, and insulin and endometrial cancer risk. Br J Cancer 2003;89:1697–1704.
31.
Lukanova A, Zeleniuch-Jacquotte A, Lundin E, Micheli A, Arslan AA, Rinaldi S, Muti P, Lenner P, Koenig KL, Biessy C, Krogh V, Riboli E, Shore RE, Stattin P, Berrino F, Hallmans G, Toniolo P, Kaaks R: Prediagnostic levels of C-peptide, IGF-I, IGFBP-1, -2, and -3 and risk of endometrial cancer. Int J Cancer 2004;108:262–268.
32.
Khandwala HM, McCutcheon IE, Flyvbejerg A, Friend KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 2000;21:215–244.
33.
Maiorano E, Loverro G, Viale G, Giannini T, Napoli A, Perlino E: Insulin-like growth factor-I expression in normal and diseased endometrium. Int J Cancer 1999;80:188–193.
34.
Franceschi S, Barbone F, Negri E, Decarli A, Ferraroni M, Filiberti R, Giacosa A, Gnagnarella P, Nanni O, Salvini S, et al: Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients. Ann Epidemiol 1995;5:69–75.
35.
Brismar K, Hilding A, Lindgren B: Regulation of IGFBP-1 in humans. Prog Growth Factor Res 1995;6:449–456.
36.
Weaver JU, Holly JM, Kopelman PG, Noonan K, Giadom CG, White N, Virdee S, Wass JA: Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. Clin Endocrinol (Oxf) 1990;33:415–422.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.