ArticlesCirculating concentrations of insulin-like growth factor I and risk of breast cancer
Introduction
There is substantial experimental evidence that the growth hormone/insulin-like growth factor (IGF)-I axis not only affects the proliferative behaviour of breast cancer,1, 2, 3 but also stimulates proliferation of normal breast epithelial cells.4 Transgenic mice that overexpress growth hormone have a high frequency of breast cancer, and overexpression of IGF-I-receptor agonists is associated with cancer and incomplete mammary involution.5, 6, 7 Similarly, rhesus monkeys treated with growth hormone or IGF-I have mammary gland hyperplasia.4 By contrast, ductal hypoplasia is seen in animals that overexpress a growth-hormone antagonist.8, 9 Studies in mice have shown a positive correlation between the strain-specific incidence of breast cancer and the activity of the growth hormone/IGF-I axis.10
There is a large variation between individuals in circulating concentrations of IGF-I and IGF binding protein 3 (IGFBP-3)—the principal IGFBP in the circulation.11, 12 The effect of IGF-I on the proliferation of breast epithelial cells and evidence that increased turnover in certain epithelial-cell populations is associated with a greater risk of neoplastic transformation, led us to investigate the relation of circulating IGF-I concentrations and the risk of breast cancer in women.4, 13
Section snippets
Methods
We carried out a nested case-control study within the Nurses' Health Study cohort. The Nurses' Health Study started in 1976 when 121 700 female registered nurses aged 30–55 years completed and returned a mailed questionnaire. The cohort is assessed every 2 years by questionnaire to update exposure status and to identify newly diagnosed disease. Data have been collected about breast-cancer risk factors such as height, weight, age at menarche, menopause, and at the birth of their first child,
Results
Baseline characteristics of the cases and controls, by menopausal status, are shown in table 1. The mean time between blood collection and diagnosis was 28 months (SD 16) with a range of 1–57 months.
There was a significant relation between IGF-I and age (r=−0·12, p=0·01). IGF-I concentrations did not differ between cases and controls in the whole cohort or among postmenopausal women (table 2). Among premenopausal women younger than 50 years, the mean IGF-I concentration was significantly higher
Discussion
To our knowledge this is the first prospective study to investigate the relation between circulating IGF-I concentrations and risk of breast cancer. We observed a strong positive relation among premenopausal women, particularly after adjusting for concentrations of IGFBP-3, but no association among postmenopausal women.
Two case-control studies18, 21 also found a positive relation between plasma IGF-I concentrations. In the larger study,18 the relation was strongest among premenopausal women
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