Background: Components of the insulin-like growth factor (IGF) system have been associated with several cancers, but very few studies are available for ovarian cancer. Methods: A case-control study conducted between 1999 and 2003 in Italy, including a total of 59 women with incident, histologically confirmed ovarian cancer and 108 controls admitted to the same hospital network as cases, for acute non-neoplastic diseases. All subjects were interviewed using a validated questionnaire. Results: After adjustment for potential confounders, the multivariate odds ratios for the highest versus the lowest tertile of various IGF components were 0.6 (95% confidence interval, CI: 0.2–1.4) for free IGF-I, 0.4 (CI: 0.1–1.5) for total IGF-I, 2.6 (CI: 0.9–6.9) for IGF-binding protein (IGFBP)-1, and 0.2 (CI: 0.0–0.6) for IGFBP-3. Conclusions: This study suggests a protective role of IGFBP-3 and a positive association of IGFBP-1 with ovarian cancer. The complex role of the IGF system in ovarian carcinogenesis deserves further clarification.

1.
Riman T, Persson I, Nilsson S: Hormonal aspects of epithelial ovarian cancer: Review of epidemiological evidence. Clin Endocrinol (Oxf) 1998;49:695–707.
2.
La Vecchia C: Epidemiology of ovarian cancer: A summary review. Eur J Cancer Prev 2001;10:125–129.
3.
Chiaffarino F, Pelucchi C, Parazzini F, Negri E, Franceschi S, Talamini R, Conti E, Montella M, La Vecchia C: Reproductive and hormonal factors and ovarian cancer. Ann Oncol 2001;12:337–341.
4.
Risch HA: Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 1998;90:1774–1786.
5.
Karasik A, Menczer J, Pariente C, Kanety H: Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endocrinol Metab 1994;78:271–276.
6.
Beck EP, Russo P, Gliozzo B, Jaeger W, Papa V, Wildt L, Pezzino V, Lang N: Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue. Gynecol Oncol 1994;53:196–201.
7.
Hofmann J, Wegmann B, Hackenberg R, Kunzmann R, Shulz KD, Haveman K: Production of insulin-like growth factor binding proteins by human ovarian carcinoma cells. J Cancer Res Clin Oncol 1994;120:137–142.
8.
Flyvbjerg A, Mogensen O, Mogensen B, Nielsen OS: Elevated serum insulin-like growth factor-binding protein 2 (IGFBP-2) and decreased IGFBP-3 in epithelial ovarian cancer: Correlation with cancer antigen 125 and tumor-associated trypsin inhibitor. J Clin Endocrinol Metab 1997;82:2308–2313.
9.
Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Zeleniuch-Jacquotte A, Berrino F, Hallmans G, Riboli E, Kaaks R: Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer 2002;101:549–554.
10.
Lukanova A, Lundin E, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Riboli E, Hallmans G, Berrino F, Zeleniuch-Jacquotte A, Toniolo P, Kaaks R: Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy). Cancer Causes Control 2003;14:285–292.
11.
Franceschi S, Barbone F, Negri E, Decarli A, Ferraroni M, Filiberti R, Giacosa A, Gnagnarella P, Nanni O, Salvini S: Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients. Ann Epidemiol 1995;5:69–75.
12.
Thierry van Dessel HJHM, Chandrasekher Y, Yap OWS, Lee PDK, Hintz RL, Faessen GHJ, Braat DDM, Fauser BCJM, Giudice LC: Serum and follicular fluid levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF-binding protein-1 and -3 during the normal menstrual cycle. J Clin Endocrinol 1996;81:1224–1231.
13.
LeRoith D, Roberts CT Jr: The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127–137.
14.
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.
15.
Klotz DM, Hewitt SC, Ciana P, Raviscioni M, Lindzey JK, Foley J, Maggi A, DiAugustine RP, Korach KS: Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. J Biol Chem 2002;277:8531–8537.
16.
Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG: A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991;72:83–89.
17.
Plymate SR, Hoop RC, Jones RE, Matej LA: Regulation of sex hormone-binding globulin production by growth factors. Metabolism 1990;39:967–970.
18.
Katsaros D, Yu H, Levesque MA, Danese S, Genta F, Richiardi G, Fracchioli S, Khosravi MJ, Diamandi A, Gordini G, Diamandis EP, Massobrio M: IGFBP-3 in epithelial ovarian carcinoma and its association with clinico-pathological features and patient survival. Eur J Cancer 2001;37:478–485.
19.
Juul A, Scheike T, Pedersen AT, Main KM, Andersson AM, Pedersen LM, Skakkebaek NE: Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle. Hum Reprod 1997;12:2123–2128.
20.
Underwood LE, Thissen JP, Lemozy S, Ketelslegers JM, Clemmons DR: Hormonal and nutritional regulation of IGF-I and its binding proteins. Horm Res 1994;42:145–151.
21.
Lee PD, Giudice LC, Conover CA, Powell DR: Insulin-like growth factor binding protein-1:Recent findings and new directions. Proc Soc Exp Biol Med 1997;216:319–357.
22.
Elgin RG, Busby WH Jr, Clemmons DR: An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Proc Natl Acad Sci USA 1987;84:3254–3258.
23.
Busby WH, Hossenlopp P, Binoux M, Clemmons DR: Purified preparations of the amniotic fluid-derived insulin-like growth factor-binding protein contain multimeric forms that are biologically active. Endocrinology 1989;125:773–777.
24.
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.
25.
Augustin LSA, Dal Maso L, Franceschi S, Talamini R, Kendall CWC, Jenkins DJA, Vidgen E, Martini P, La Vecchia C: Association between components of the insulin-like growth factor (IGF) system and endometrial cancer risk. Oncology 2004;67:54–59.
26.
McKeown-Eyssen G: Epidemiology of colorectal cancer revisited: Are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 1994;3:687–695.
27.
Giovannucci E: Insulin and colon cancer. Cancer Causes Control 1995;6:164–179.
28.
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.
29.
Kaaks R, Lukanova A: Energy balance and cancer: The role of insulin and insulin-like growth factor-I. Proc Nutr Soc 2001;60:91–106.
30.
Tran TT, Medline A, Bruce RW: Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev 1996;5:1013–1015.
31.
Augustin LS, Franceschi S, Jenkins DJ, Kendall CW, La Vecchia C: Glycemic index in chronic disease: A review. Eur J Clin Nutr 2002;56:1049–1071.
32.
Holmes MD, Pollak MN, Hankinson SE: Lifestyle correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev 2002;11:862–867.
33.
Holmes MD, Pollak MN, Willett WC, Hankinson SE: Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev 2002;11:852–861.
34.
Giovannucci E, Pollack M, Liu Y, Platz EA, Mjeed N, Rimm EB, Willett WC: Nutritional predictors of insulin-like growth factor I and their relationship to cancer in men. Cancer Epidemiol Biomarkers Prev 2003;12:84–89.
35.
Bidoli E, La Vecchia C, Montella M, Dal Maso L, Conti E, Negri E, Scarabelli C, Carbone A, Decarli A, Franceschi S: Nutrient intake and ovarian cancer: An Italian case-control study. Cancer Causes Control 2002;13:255–261.
36.
Augustin LS, Polesel J, Bosetti C, Kendall CW, La Vecchia C, Parpinel M, Conti E, Montella M, Franceschi S, Jenkins DJ, Dal Maso L: Dietary glycemic index, glycemic load and ovarian cancer risk: A case-control study in Italy. Ann Oncol 2003;14:78–84.
37.
Rodriguez C, Calle EE, Fakhrabadi-Shokoohi D, Jacobs EJ, Thun MJ: Body mass index, height, and the risk of ovarian cancer mortality in a prospective cohort of postmenopausal women. Cancer Epidemiol Biomarkers Prev 2002;11:822–828.
38.
Dal Maso L, Franceschi S, Negri E, Conti E, Montella M, Vaccarella S, Canzonieri V, Parazzini F, La Vecchia C: Body size indices at different ages and epithelial ovarian cancer risk. Eur J Cancer 2002;38:1769–1774.
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