title: 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/m(2). Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense tissue area of 48.3 (SD: 33.3) cm(2) . 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 (p(trend) = 0.03 and 0.09, respectively) and nondense tissue areas (p(trend) < 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.
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Rinaldi
authors.forename: C
authors.initials: C
authors.lastname: Biessy
authors.forename: M
authors.initials: M
authors.lastname: Hernandez
authors.forename: F
authors.initials: F
authors.lastname: Lesueur
authors.forename: I
authors.initials: I
authors.lastname: dos-Santos-Silva
authors.forename: M S
authors.initials: MS
authors.lastname: Rice
authors.forename: M
authors.initials: M
authors.lastname: Lajous
authors.forename: R
authors.initials: R
authors.lastname: Lopez-Ridaura
authors.forename: G
authors.initials: G
authors.lastname: Torres-Mejía
authors.forename: I
authors.initials: I
authors.lastname: Romieu
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D000071060:Breast Density; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000473:pathology; D008327:Mammography; D008800:Mexico; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause; D011379:Prognosis; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: IGF; Mexican premenopausal women; genetic polymorphisms; mammographic density
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