Skip to main content

Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case–control study



Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC).


A case–control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case.


Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58–1.62) or GCT (OR 1.13, 95% CI 0.51–2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85–1.43) or GCT (OR 0.93, 95% CI 0.68–1.28).


Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. Chen VW, Ruiz B, Killeen JL, Cote TR, Wu XC, Correa CN (2003) Pathology and classification of ovarian tumours. Cancer 97(10 Suppl):2631–2642

    PubMed  Article  Google Scholar 

  2. Chen T, Surcel HM, Lundin E, Kaasila M, Lakso HA, Schock H, Kaaks R, Koskela P, Grankvist K, Hallmans G, Pukkala E, Zeleniuch-Jacquotte A, Toniolo P, Lehtinen M, Lukanova A (2011) Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 20(2):324–336

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  4. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353

    PubMed  Article  CAS  Google Scholar 

  5. 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 (2002) Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer 101(6):549–554

    PubMed  Article  CAS  Google Scholar 

  6. Peeters PH, Lukanova A, Allen N, Berrino F, Key T, Dossus L et al (2007) Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 14(1):81–90

    PubMed  Article  CAS  Google Scholar 

  7. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    PubMed  Article  CAS  Google Scholar 

  8. McSorley MA, Alberg AJ, Allen DS, Allen NE, Brinton LA, Dorgan JF, Pollak M, Tao Y, Helzlsouer KJ (2007) C-reactive protein concentrations and subsequent ovarian cancer risk. Obstet Gynecol 109(4):933–941

    PubMed  Article  CAS  Google Scholar 

  9. Lundin E, Dossus L, Clendenen T, Krogh V, Grankvist K, Wulff M, Sieri S, Arslan AA, Lenner P, Berrino F, Hallmans G, Zeleniuch-Jacquotte A, Toniolo P, Lukanova A (2009) C-reactive protein and ovarian cancer: a prospective study nested in three cohorts (Sweden, USA, Italy). Cancer Causes Control 20(7):1151–1159

    PubMed  Article  Google Scholar 

  10. Toriola AT, Grankvist K, Agborsangaya CB, Lukanova A, Lehtinen M, Surcel HM (2011) Changes in pre-diagnostic serum C-reactive protein concentrations and ovarian cancer risk: a longitudinal study. Ann Oncol. (In press)

  11. Lehtinen M, Koskela P, Ogmundsdottir HM, Bloigu A, Dillner J, Gudnadottir M, Hakulinen T, Kjartansdottir A, Kvarnung M, Pukkala E, Tulinius H, Lehtinen T (2003) Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring. Am J Epidemiol 158(3):207–213

    PubMed  Article  Google Scholar 

  12. Gissler M, Teperi J, Hemminki E, Merilainen J (1995) Data quality after restructuring a national medical registry. Scand J Soc Med 23(1):75–80

    PubMed  CAS  Google Scholar 

  13. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21:215–244

    PubMed  Article  CAS  Google Scholar 

  14. Magoffin DA, Weitsman SR (1993) Insulin-like growth factor-I stimulates the expression of 3-hydroxysteroid dehydrogenase messenger ribonucleic acid in ovarian theca-interstitial cells. Biol Reprod 48:1166–1173

    PubMed  Article  CAS  Google Scholar 

  15. Plymate SR, Hoop RC, Jones RE, Matej LA (1990) Regulation of sex hormone-binding globulin production by growth factors. Metabolism 39:967–970

    PubMed  Article  CAS  Google Scholar 

  16. Ness RB, Cottreau C (1999) Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91(17):1459–1467

    PubMed  Article  CAS  Google Scholar 

  17. Horn-Ross PL, Whittemore AS, Harris R, Itnyre J (1992) Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. VI. Nonepithelial cancers among adults. Collaborative Ovarian Cancer Group. Epidemiology 3(6):490–495

    PubMed  Article  CAS  Google Scholar 

Download references


This research was supported by the National Cancer Institute at the National Institutes of Health. The funding source had no role in the study design, interpretation of data, and publication of results. This study was conducted while Adetunji T Toriola was at the National Institute for Health and Welfare, Finland. He was supported by a European Association for Cancer Research (EACR) Travel Fellowship Award to visit the Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg. The authors are indebted to Yelena Afanasyeva, Pirjo Kontiokari, Annika Uimonen, and Sara Kuusiniemi for their excellent technical assistance in the conduct of the study.

Conflict of interest

None declared.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Adetunji T. Toriola.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Toriola, A.T., Surcel, HM., Lundin, E. et al. Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case–control study. Cancer Causes Control 22, 1607 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Insulin-like growth factor (IGF-I)
  • C-reactive protein (CRP)
  • Pregnancy
  • Non-epithelial ovarian cancer
  • Nested case–control study