Endometrial Cancer and the IGF System: A Case-Control Study in Greece

Abstract

Objectives: Insulin-like growth factor I (IGF-I) and other components of the IGF system have been implicated in the etiology of several human malignancies. We have undertaken a case-control study among Greek women to explore the relation of major components of the IGF system (IGF-I, IGF-II and IGF-binding protein 3, IGFBP-3) with endometrial cancer risk. Methods: During a 1-year period (1999), 84 incident cases of histologically confirmed endometrial cancer were compared with 84 control women admitted to the same clinical department for small gynecological operations, mainly pelvic prolapse. Data were modeled through multiple logistic regression. Results: Endometrial cancer was positively associated with IGF-II and inversely with IGF-I. Both associations were statistically significant and they appear symmetrical around the null value. IGFBP-3 is positively associated with endometrial cancer risk, but this association does not reach statistical significance. Conclusions: This study adds to the gradually developing consensus that components of the IGF system play a central role in human carcinogenesis. It is possible that IGF-II, rather than IGF-I, is closely linked to the etiology of endometrial cancer, the form of cancer most strongly associated with obesity.

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

“…It is also possible that cleaved IGFBP-3 fragments may either promote or inhibit tumor growth (35). We have used a previously validated and reliable assay (22,23) to measure IGFBP-3. Other IGFBPs have been studied less extensively.…”

“…Measurements of serum leptin (Diagnostic Systems Laboratories, Webster, TX, USA), insulin, IGF-I, IGF-II, IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, and GHBP (LINCO, St Louis, MO, USA) were obtained for all samples from a single run of commercially available radioimmunoassays and ELISAs in the principal investigator's laboratory at the Beth Israel Deaconess Medical Center as described previously (22,23). For the newly studied markers IGFBP-4, IGFBP-6, and GHBP, we report the following assay characteristics: IGFBP-4 had a sensitivity of 0.008 ng/ml and intraassay coefficient of variation (CV) values of 3.0-6.3%, IGFBP-6 had a sensitivity of 1.1 ng/ml and intraassay CV values of 6.4-10.7%, and GHBP had a sensitivity of 1.69 pmol/l and intraassay CV values of 3.2-5.6%.…”

Does IGF-1 play a role in the biology of endometrial cancer?

“…However, these studies are scarce and the results remain inconsistent (Table 3) [10,[28][29][30][31][32][33][34][35]. Four studies found no association between serum IGF-1 and EC biology [10,[28][29][30].…”

“…Some studies detected statistically significantly lower or higher serum IGF-1 levels in women with EC as compared to healthy controls [31][32][33][34][35]51].…”

“…Four teams found statistically significantly lower IGF-1 levels in subjects with EC as compared to healthy women [31][32][33][34][35]51], but they did not account for the possibility of cardiovascular diseases in the investigated populations (common in older, postmenopausal patients), what might be a serious study limitation due to a proven link between lowered serum IGF-1 level and these pathologies [40,42].…”