The Vitamin D Pathway and Mammographic Breast Density in Postmenopausal Women

描述(申请人提供)：绝经后妇女的维生素D途径和乳房X光摄影研究摘要实验室研究表明，维生素D具有多种化学预防特性。然而，探讨维生素D对乳腺癌风险的影响的流行病学数据是有限的，而且不一致。虽然许多研究已经评估了饮食摄入量，但直接测量血液中维生素D水平与乳腺癌风险相关的研究较少。没有人在其他分子的完整背景下研究维生素D，如视黄醇，实验室研究表明，这种分子会影响维生素D对乳房细胞的作用。此外，具有化学预防或有丝分裂特性的维生素D的下游靶点，如甲状旁腺激素和IGF-1，本身可能会影响乳腺癌的风险。这项研究的目的是评估维生素D途径与乳房X光检查乳房密度的关系，乳房密度是乳腺癌风险的中间标志。我们建议1)检查乳房X光检查密度和血液维生素D水平之间的关系；2)确定甲状旁腺激素、IGF-1和IGFBP-3在调节维生素D和密度之间的关联中的潜在作用；以及3)确定乳房X光检查密度和维生素D之间的关系是否被血液中视黄醇或钙的水平所改变。为了实现这些目标，我们建议在我们现有的研究中增加额外的暴露评估，评估270名在威斯康星大学麦迪逊诊所接受筛查乳房X光检查的健康绝经后女性的乳房密度。这项现有研究的数据收集包括乳腺癌风险因素问卷和血液样本，两者都是在乳房X光检查时获得的。使用计算机辅助方法(Cumulus软件)，将乳腺X光摄影密度评估为测量百分比密度的连续线性函数。我们建议通过测量血清维生素D[25(OH)D]、甲状旁腺激素、IGF-1、IGFBP-3、视黄醇和钙的水平来补充这项现有的研究。统计方法将用于确定钼靶密度与维生素D的关系，甲状旁腺激素、IGF-1和IGFBP-3的潜在调节作用，以及视黄醇和钙的潜在调节作用。将维生素D暴露评估添加到母体研究中将有效地利用现有研究资金的投资。通过使用连续尺度上的乳房X光照相密度作为中间标记，本研究提供了一种高效的设计，具有强大的能力来检测乳房密度与潜在重要和可修饰的维生素D途径分子水平之间的关联。由于维生素D缺乏在美国很普遍，而且还在增加，阐明维生素D与乳腺癌风险的相关性的证据可能会指出预防乳腺癌的重要策略。 公共卫生相关性： 绝经后妇女的维生素D途径和乳房X光摄影研究叙事实验室的研究表明，维生素D具有抗癌特性，乳房组织中含有维生素D受体。我们计划测量270名女性的血液中维生素D和其他与维生素D相互作用的分子的水平，这些女性已经参加了乳房X光检查乳房密度的研究。由于乳房密度是乳腺癌风险的一个强有力的中间标志，维生素D和乳房密度之间的关联将表明维生素D在预防乳腺癌方面具有潜在的作用。

DESCRIPTION (provided by applicant): The Vitamin D Pathway and Mammographic Breast Density in Postmenopausal Women Abstract Laboratory studies have demonstrated that Vitamin D has a number of chemopreventive properties. However, epidemiologic data exploring the effects of Vitamin D on breast cancer risk are limited and inconsistent. While many studies have assessed dietary intake, fewer have directly measured blood levels of Vitamin D in relation to breast cancer risk. None have explored Vitamin D in the full context of other molecules, such as retinol, which laboratory studies suggest influence the effect of Vitamin D on breast cells. Further, downstream targets of Vitamin D with chemopreventive or mitogenic properties, such as parathyroid hormone and IGF-1, may themselves influence breast cancer risk. The objective of this study is to evaluate the Vitamin D pathway in relation to mammographic breast density, an intermediate marker of breast cancer risk. We propose to 1) examine the relation between mammographic density and blood levels of Vitamin D; 2) determine the potential role of parathyroid hormone, IGF-1, and IGFBP-3 in mediating the association between Vitamin D and density; and 3) determine if the relation between mammographic density and Vitamin D is modified by blood levels of retinol or calcium. To accomplish these aims, we propose to add additional exposure assessment to our existing research study evaluating breast density among 270 healthy postmenopausal women attending University of Wisconsin-Madison Clinics for a screening mammogram. Data collection for this existing study includes a breast cancer risk factor questionnaire and a blood sample, both obtained at the time of the mammogram. Mammographic density will be assessed as a continuous linear function measuring percent density, using a computer-assisted method (Cumulus software). We propose to supplement this existing study by measuring serum levels of Vitamin D [25(OH)D], parathyroid hormone, IGF-1, IGFBP-3, retinol, and calcium. Statistical methods will be used to determine the relation between mammographic density and Vitamin D, the potential mediating roles of parathyroid hormone, IGF-1, and IGFBP-3, and the potential modifying effects of retinol and calcium. Adding Vitamin D exposure assessment to the parent study will effectively leverage existing investment of research funds. By using mammographic density on a continuous scale as an intermediate marker, this study offers an efficient design with strong power to detect an association between breast density and levels of potentially important and modifiable Vitamin D pathway molecules. Since Vitamin D insufficiency in the United States is widespread and increasing, evidence elucidating the relevance of Vitamin D to breast cancer risk may point to important strategies for breast cancer prevention. PUBLIC HEALTH RELEVANCE: The Vitamin D Pathway and Mammographic Breast Density in Postmenopausal Women Narrative Laboratory studies have demonstrated that Vitamin D has anti-carcinogenic properties, and breast tissue is known to contain Vitamin D receptors. We plan to measure blood levels of Vitamin D and other molecules which interact with Vitamin D in a group of 270 women who are already enrolled in a study of mammographic breast density. Since breast density is a strong intermediate marker of breast cancer risk, an association between Vitamin D and breast density would suggest a potential role for Vitamin D in the prevention of breast cancer.