A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

Abstract

The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case -control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74 -3.95; test for linear trend, P ¼ 0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21 -1.12, P for trend ¼ 0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre-or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer. It is well established that insulin-like growth factor-I (IGF-I) and IGF-II can stimulate cell proliferation and inhibit cell death in many tissue types (Pollak, 2000) including normal and malignant breast cancer cells (Sachdev and Yee, 2001). The bioavailability of circulating IGF ligands is complex; at least six IGF-binding proteins (IGFBPs) have been identified, the most abundant of which is IGFBP-3. This binds approximately 75 -90% of circulating IGF-I and IGF-II and may be the most important determinant of IGF bioavailability (Jones and Clemmons, 1995).There is considerable between-person variation in the circulating concentrations of IGF-I, IGF-II and their binding proteins, believed to be due to genetic and environmental factors (Jones and Clemmons, 1995;Harrela et al, 1996). This variation may be important because epidemiological evidence suggests that elevated levels of serum IGF-I, as absolute concentrations or relative to IGFBP-3, may be associated with an increased risk of breast cancer in premenopausal women (Peyrat et al, 1993;Bruning et al, 1995;Bohlke et al, 1998;Hankinson et al, 1998;Petridou et al, 2000;Toniolo et al, 2000;Kaaks et al, 2002;Krajcik et al, 2002;Muti et al, 2002;Yu et al, 2002;Keinan-Boker et al, 2003). There are limited data on the association between serum IGF-II concentration and breast cancer risk (Holdaway et al, 1999;Li et al, 2001;Yu et al, 2002;Gr nbaek et al, 2004).The aim of this study is to examine the associations between serum concentrations of IGF-I, IGF-II and IGFBP-3 and subsequent breast cancer risk in a case -control study nested within a cohort of women on the island of Guernsey. MATERIALS AND METHODS The Guernsey cohortBetween 1977 and 1991, 6127 women aged 35 years or older who lived on the British island of Guernsey were re...

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

“…Thus, since our study population consisted primarily of postmenopausal women, it is not surprising that we detected no relationship between IGF-I and breast cancer risk. We also did not find any association between IGF-II and risk of breast cancer, as has been reported previously (7). However, evidence from animal and cell line experiments examining the role of IGF-II in carcinogenesis indicates increased rates of malignancies, including breast tumors (28)(29)(30)(31)(32)(33), and results from one case-control study found a positive association between IGF-II and ER-positive but not ER-negative breast cancer among postmenopausal women (9).…”

“…These analyses also took into account potential effects of hyperinsulinemia, by including insulin and leptin, which we show to have no independent associations with breast cancer of their own accord. Serum IGF-I appears to be associated with risk of breast cancer among premenopausal women (7,10,12,13,15,17,24,25), but no similar association has been found among postmenopausal women (10,26). Several explanations for this dichotomy have been proposed.…”

“…Numerous epidemiologic studies have examined the association between components of the IGF system, in particular IGF-I and IGFBP-3, and female breast cancer (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Most nested case-control studies have demonstrated an increased risk of premenopausal breast cancer with higher concentrations of IGF-I, but results have been mixed with respect to IGFBP-3, with reports of positive, negative, and no association.…”

Calcium intake and breast cancer risk: meta-analysis of prospective cohort studies

“…We considered several possible explanations for this difference. First, the complex interactions among Ca, vitamin D and insulin-like growth factors may promote growth inhibition in breast cancer cells (13,49) . Second, Ca may serve as a potential regulator in oestrogen-driven cell proliferation (50) .…”

Posibles mecanismos de acción biológica de la actividad física en el cáncer de mama

“…De hecho, se ha demostrado que el estradiol acentúa la expresión de la IGF-I y los receptores de ambas hormonas, dando como resultado una interacción sinérgica que estimula la proliferación de células de cáncer de mama (Allen et al, 2005).…”