title: Influence of insulin-like growth factors on the strength of the relation of vitamin D and calcium intakes to mammographic breast density.
abstract: Diets with higher vitamin D and calcium contents were found associated with lower mammographic breast density and breast cancer risk in premenopausal women. Because laboratory studies suggest that the actions of vitamin D, calcium, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 (IGFBP-3) on human breast cancer cells are interrelated, we examined whether IGF-I and IGFBP-3 levels could affect the strength of the association of vitamin D and calcium intakes with breast density. Among 771 premenopausal women, breast density was measured by a computer-assisted method, vitamin D and calcium intakes by a food frequency questionnaire, and levels of plasma IGF-I and IGFBP-3 by ELISA methods. Multivariate linear regression models were used to examine the associations and the interactions. The negative associations of vitamin D or calcium intakes with breast density were stronger among women with IGF-I levels above the median (beta = -2.8, P = 0.002 and beta = -2.5, P = 0.002, respectively) compared with those with IGF-I levels below or equal to the median (beta = -0.8, P = 0.38 and beta = -1.1, P = 0.21; P(interaction) = 0.09 and 0.16, respectively). Similar results were observed within levels of IGFBP-3 (P(interaction) = 0.06 and 0.03, respectively). This is the first study to report that the negative relation of vitamin D and calcium intakes with breast density may be seen primarily among women with high IGF-I or high IGFBP-3 levels. Our findings suggest that the IGF axis should be taken into account when the effects of vitamin D and calcium on breast density (and perhaps breast cancer risk) are examined at least among premenopausal women.
authors.affiliation: Unité de recherche en santé des populations, Centre hospitalier affilié universitaire de Québec, Québec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Diorio
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bérubé
authors.forename: Celia
authors.initials: C
authors.lastname: Byrne
authors.forename: Benoît
authors.initials: B
authors.lastname: Mâsse
authors.forename: Nicole
authors.initials: N
authors.lastname: Hébert-Croteau
authors.forename: Martin
authors.initials: M
authors.lastname: Yaffe
authors.forename: Gary
authors.initials: G
authors.lastname: Coté
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Jacques
authors.initials: J
authors.lastname: Brisson
mesh_terms: D000328:Adult; D001940:Breast / Q000033:anatomy & histology* / Q000378:metabolism*; D002118:Calcium / Q000008:administration & dosage*; D004032:Diet; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008327:Mammography; D008875:Middle Aged; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D014807:Vitamin D; D007334:Insulin-Like Growth Factor I; D002118:Calcium