Diorio Caroline, Bérubé Sylvie, Byrne Celia, Mâsse Benoît, Hébert-Croteau Nicole, Yaffe Martin, Coté Gary, Pollak Michael, Brisson Jacques
Unité de recherche en santé des populations, Centre hospitalier affilié universitaire de Québec, Québec, Canada.
Cancer Res. 2006 Jan 1;66(1):588-97. doi: 10.1158/0008-5472.CAN-05-1959.
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.
研究发现，维生素D和钙含量较高的饮食与绝经前女性较低的乳腺钼靶密度及乳腺癌风险相关。由于实验室研究表明，维生素D、钙、胰岛素样生长因子（IGF）-I和IGF结合蛋白-3（IGFBP-3）对人乳腺癌细胞的作用相互关联，因此我们研究了IGF-I和IGFBP-3水平是否会影响维生素D和钙摄入量与乳腺密度之间关联的强度。在771名绝经前女性中，采用计算机辅助方法测量乳腺密度，通过食物频率问卷评估维生素D和钙摄入量，并用酶联免疫吸附测定法检测血浆IGF-I和IGFBP-3水平。使用多变量线性回归模型来研究这些关联和相互作用。与IGF-I水平低于或等于中位数的女性相比（β = -0.8，P = 0.38；β = -1.1，P = 0.21；交互作用P值分别为0.09和0.16），IGF-I水平高于中位数的女性中，维生素D或钙摄入量与乳腺密度的负相关更强（β分别为 -2.8，P = 0.002；β = -2.5，P = 0.002）。在IGFBP-3水平分组中也观察到了类似结果（交互作用P值分别为0.06和0.03）。这是第一项报告维生素D和钙摄入量与乳腺密度之间的负相关可能主要见于IGF-I或IGFBP-3水平较高女性的研究。我们的研究结果表明，至少在绝经前女性中，在研究维生素D和钙对乳腺密度（以及可能的乳腺癌风险）的影响时，应考虑IGF轴。
