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¹ Channing Laboratory, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston 02115, Massachusetts, USA
² Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
³ LBI-ACR VIEnna and ACR-ITR VIEnna, Vienna, Austria
⁴ Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USA
⁵ University Department of Clinical Science at North Bristol, Southmead Hospital, Bristol, UK
⁶ Departments of Medicine and Oncology, McGill University, Montre 'al, Que 'bec, Canada

(Correspondence should be addressed to E S Schernhammer; Email: eva.schernhammer{at}channing.harvard.edu)

Both insulin-like growth factors (IGF) and body size have been linked to premenopausal breast cancer risk. However, observational studies of IGF have not been consistent, and they suggest that perhaps earlier levels of IGF might be more strongly related to breast cancer than those measured at mid-age. We therefore sought to explore associations between several measures of body size throughout life and IGF levels in premenopausal women. We examined cross-sectional associations of birth weight, body shape (or somatotype) at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, bra cup size at age 20, adult waist circumference and waist-to-hip ratio (WHR), and attained height with plasma levels of IGF-I, IGF binding protein 3 (IGFBP-3), IGFBP-1, and GH. Participants were 592 healthy premenopausal women aged 34–52 from the Nurses’ Health Study II. Using multiple linear regression, we computed least-square mean hormone levels across the categories of early life anthropometric factors. We observed consistent and strong inverse associations between body shape at various stages in life and IGF levels. Somatotype at ages 5 and 10 was inversely associated with IGF-I (P for difference, < 0.01) and positively with IGFBP-3 measured later in adulthood. Further, comparing women with a BMI 25 kg/m² at age 18 vs < 19 kg/m², similar associations were observed for IGF-I (P for trend, 0.005) and IGFBP-3 (P for trend, 0.01), which were even stronger for BMI at blood collection (BMI< 20 versus BMI 30, mean IGF-I 254 ng/ml, 95% CI, 239–271 vs 208 ng/ml, 95% CI, 195–222). Both waist circumference and WHR were strongly and inversely related to IGFBP-1 levels (top versus bottom quartile of waist circumference: 14.5 vs 40.0 ng/ml, P for trend 0.0005; WHR: 18.3 vs 39.4 ng/ml, P for trend 0.002), with similar results for bra cup size at age 20 although they did not reach statistical significance. There was no association between height and IGF or GH levels. Birth weight, on the other hand, was weakly positively associated with both IGF-I and IGFBP-1 levels, and inversely with GH. Our results suggest that childhood and adult body size may affect premenopausal breast cancer risk differently than birth weight, through associations with IGF and GH levels.

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