Predictors of Mammary Gland Development & Breast Fibroglandular Volume at puberty

描述(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，乳腺癌发病率的许多国际差异不能用已知或怀疑的危险因素来解释。人们的注意力已经转移到女性生命的早期阶段，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，跨越了几十年，这使得前瞻性研究很难完成。乳腺发育早和乳房密度高与乳腺癌风险增加有关，可以作为乳腺癌风险的早期推定标记。高比例的乳房放射学致密区域是已知的乳腺癌最强烈的危险因素之一，可能在青春期乳房发育时确定。我们建议使用一个现有的约515名出生于2002年的智利青春期前女孩的队列来研究乳腺癌风险的假定早期标记物，特别是乳腺发育(TANER阶段2)和DXA在TANER阶段4测量的致密乳腺组织体积与一些前因之间的关系：内分泌干扰物，特别是双酚A和邻苯二甲酸酯；频繁食用高脂肪乳制品和红肉；血液中炎症标记物的水平，特别是白细胞介素6、肿瘤坏死因子和C反应蛋白；全球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.