Circulating concentrations of insulin‐like growth factor‐I, insulin‐like growth factor‐binding protein‐3, genetic polymorphisms and mammographic density in premenopausal Mexican women: Results from the ESMaestras cohort

Abstract

The insulin-like growth factor (IGF) axis plays an essential role in the development of the mammary gland. High circulating levels of IGF-I and of its major binding protein IGFBP3 have been related with increased mammographic density in Caucasian premenopausal women. Some common single nucleotide polymorphisms (SNPs) in genes of the IGF pathway have also been suggested to play a role in mammographic density. We conducted a cross-sectional study nested within the large Mexican ESMaestras cohort, to investigate the relation between circulating levels of IGF-I, IGFBP-3, the IGF-I/IGFBP-3 ratio, five common SNPs in the IGF-1, IGFBP-3 and IGF-1R genes, and mammographic density in 593 premenopausal Mexican women. Mean age at mammogram was 43.1 (standard deviation–SD=3.7) years, and average body mass index (BMI) at recruitment was 28.5 kg/m2. Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense tissue area of 48.3 (SD: 33.3) cm2. Mean IGF-I and IGFBP-3 concentrations were 15.33 (SD: 5.52) nmol/l and 114.96 (SD: 21.34) nmol/l, respectively. No significant associations were seen between percent density and biomarker concentrations but women with higher IGF-I and IGF-I/IGFBP-3 concentrations had lower absolute dense (ptrend =0.03 and 0.09, respectively) and non-dense tissue areas (ptrend <0.001 for both parameters). However, these associations were null after adjustment by BMI. SNPs in specific genes were associated with circulating levels of growth factors, but not with mammographic density features. These results do not support the hypothesis of a strong association between circulating levels of growth hormones and mammographic density in Mexican premenopausal women.

Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young Nulliparous Women

“…The study reveals positive associations between MRI percentwater in young women and concurrent circulating levels of IGF-I, and its molar ratio, consistent with mammography-and MRIbased findings reported by others (18,19,34), albeit not all (16,20,35), studies in premenopausal women. These associations are also in line with the reported positive association between IGF-I and breast cancer risk, albeit possibly restricted to estrogen receptor-positive tumors (9, 10), suggesting that the role of these hormones in the etiology of this cancer may be mediated through their effect on breast tissue composition at young ages.…”

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

“…Recently, no association between GH, IGF-1 and percent and absolute mammographic density was observed for either premenopausal or postmenopausal women [6], which correspond to the results ofothers [34][35][36]. Furthermore, our observation of an association between IGF-1 and percent mammographic density, mainly seen among women with higher levels of IGF-1 suggest a threshold effect.…”

Reproductive and lifestyle risk factors and mammographic density in Mexican women

“…Mammography methods were reported previously[17–19]. Briefly, a single reader measured breast density from digitized film mammograms of the craniocaudal view of the left breast using Mamgr (developed at the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine), a computer-assisted thresholding technique [20–22].…”