Breast Density, IGF-I, & Prolactin, in Four Populations

描述（由申请人提供）： 不同种族和地理位置的乳腺癌发病率差异的原因尚不清楚。该建议的重点是确定可能解释这些差异的激素特征。胰岛素样生长因子I（IGF-I）被认为是营养因素与乳腺癌之间的联系，特别是在绝经前妇女中。催乳素直接影响乳腺上皮细胞的生长，并与绝经后妇女患乳腺癌的风险有关。乳腺摄影密度是乳腺癌风险的一个强有力的预测因素，似乎与这两种激素有关。本研究的目的是比较不同乳腺癌风险的四个人群的乳腺摄影密度，研究IGF-I、IGFBP-3和催乳素与乳腺摄影密度的关系，并按种族和绝经状态分别调查这些激素与乳腺摄影密度之间的关系。所有样本和乳房X线照片都是作为先前流行病学研究的一部分在四个地点收集的：夏威夷、日本、亚利桑那州和挪威。结合这些不同研究的数据提供了检查先前观察到的关联的一致性和强度的机会。这种设计将使我们能够包括具有各种种族背景的女性，她们经历了不同的生活方式和暴露。 最终分析将包括1，520名不同种族的妇女：居住在所有四个地点的白人妇女，居住在两个地点的日本妇女，来自亚利桑那州的西班牙裔妇女，以及来自夏威夷的菲律宾人、中国人和夏威夷土著妇女。受试者的年龄范围为40 - 80岁，约60%的女性为绝经后。所有受试者都是作为以前项目的一部分招募的，从未被诊断出患有癌症，乳房X光检查没有可疑病变，并提供了有关生殖和人体测量特征的信息。对于处于黄体期的绝经前女性，在禁食过夜后采集血样，并储存在-70 ℃下。将在同一实验室使用ELISA法分析血清样本中的IGF-I、IGFBP-3和催乳素。在将四个位置的乳房X光图像扫描到同一台计算机后，一名读片员将进行计算机辅助定量乳房X光密度评估。出于质量控制目的，将一式两份分析血清样本和乳房X线照片。由于血清和乳房X线摄影分析的部分资金来自以前的项目，我们只要求提供900次血清分析和600次乳房X线摄影密度评估的资金。统计分析将包括混合模型，以探索激素水平和乳腺密度之间的关系，同时控制混杂因素和研究地点的聚类。

DESCRIPTION (provided by applicant): The reasons for differences in breast cancer incidence by ethnicity and geographic location are not well understood. The focus of this proposal is to identify hormonal characteristics that may explain these discrepancies. Insulin-like growth factor I (IGF-I) has been proposed as a link between nutritional factors and breast cancer, in particular among premenopausal women. Prolactin directly affects the growth of breast epithelium and has been associated with breast cancer risk among postmenopausal women. Mammographic densities, a strong predictor of breast cancer risk, appear to be associated with both hormones. The objectives of this project are to compare mammographic densities among four populations at different breast cancer risk, examine the relation of IGF-I, IGFBP-3, and prolactin with mammographic densities, and investigate the relation between these hormones and mammographic density separately by ethnicity and menopausal status. All samples and mammograms were collected as part of previous epidemiologic studies in four locations: Hawaii, Japan, Arizona, and Norway. Combining data from these diverse studies provides the opportunity to examine the consistency and strength of previously observed associations. This design will allow us to include women with a variety of ethnic backgrounds who have experienced different life-styles and exposures. The final analysis will include 1,520 women of different ethnicities: Caucasian women residing in all four locations, Japanese women living in two locations, Hispanic women from Arizona, and Filipino, Chinese, and Native Hawaiian women from Hawaii. The age of the subjects ranges from 40 to 80 years and approximately 60% of the women are postmenopausal. All subjects were recruited as part of previous projects, were never diagnosed with cancer, have a mammogram free of suspicious lesions, and provided information on reproductive and anthropometric characteristics. Blood samples were taken after an overnight fast, for premenopausal women during the luteal phase, and stored at -70xC. Serum samples will be analyzed in the same laboratory for IGF-I, IGFBP-3, and prolactin using an ELISA assay. After scanning the mammographic images from the four locations into the same computer, one reader will perform computer-assisted quantitative mammographic density assessment. For quality control purposes, a sample of serum samples and mammograms will be analyzed in duplicate. Because serum and mammographic analyses were partially funded by the previous projects, we are only requesting funds for 900 serum analyses and 600 mammographic density assessments. The statistical analysis will include mixed models to explore the relation between hormone levels and breast density while controlling for confounders and for clustering by study location.