Predictors of Mammary Gland Development & Breast Fibroglandular Volume at puberty

描述（由申请人提供）：乳腺癌的全球负担正在上升，使其成为全球女性发病率最高的恶性肿瘤。然而，乳腺癌发病率的大部分国际差异无法用已知或可疑的风险因素来解释。注意力已经转移到女性生命的早期，认识到青春期前乳腺组织对环境影响的特殊敏感性。在青春期之前或青春期发生的事件与乳腺癌的诊断之间有相当长的时间间隔，这使得前瞻性研究难以完成。早期乳腺发育和高乳腺密度与乳腺癌风险增加相关，可作为乳腺癌风险的早期推定标志物。高比例的乳房X光密度区域是已知的乳腺癌最强的风险因素之一，可能在青春期乳房发育时建立。我们建议使用一个现有的队列，其中包括2002年出生的约515名青春期前的智利女孩，以解决乳腺癌风险的推定早期标志物之间的关系，特别是乳腺发育的开始（坦纳2期）和在坦纳4期时通过DXA测量的致密乳腺组织体积以及一些前因：内分泌干扰化学品，特别是双酚A和邻苯二甲酸酯;经常食用高脂肪乳制品和红肉;炎症标志物的血液水平，特别是白细胞介素-6、肿瘤坏死因子和C反应蛋白;整体DNA甲基化、启动子甲基化模式和ER基因甲基化。

DESCRIPTION (provided by applicant): The global burden of breast cancer is on the rise making it the malignancy with the highest incidence among women worldwide. Yet, much of the international variation of breast cancer incidence cannot be explained with known or suspected risk factors. Attention has shifted to earlier time periods of a women's life recognizing the specil susceptibility of the prepubertal mammary gland tissue to environmental influences. The considerable time lag between events prior to or at puberty and diagnosis of breast cancer spanning several decades have made prospective studies difficult to accomplish. Early onset of mammary gland development and high breast density have been associated with an increased risk of breast cancer and can serve as early putative markers of breast cancer risk. A high proportion of radiographically dense area of the breast is one of the strongest known risk factor for breast cancer and may be established at the time of breast development at puberty. We propose to use an existing cohort of about 515 prepubertal Chilean girls born in 2002 to address the relation between putative early markers of breast cancer risk, specifically onset of mammary gland development (Tanner stage 2) and volume of dense breast tissue measured by DXA at Tanner stage 4 and a number of antecedents: endocrine-disrupting chemicals, specifically bisphenol A and phthalates; frequent consumption of high fat dairy products and red meat; blood levels of inflammatory markers, specifically interleukin-6, tumor necrosis factor, and C-reactive protein; global DNA methylation, promoter methylation pattern, and methylation of the ER gene.