Epigenetic Features of Pregnancy-Associated Breast Cancer in Hispanic Women

描述（由申请人提供）：乳腺癌（BC）的风险在怀孕后立即增加。发生在产后时期的BC具有更积极的组织病理学特征，更容易转移，并且与更差的患者结局相关。平均而言，它们也影响年轻女性，并可能占早发性乳腺癌（EOBC）的很大比例，这种现象不成比例地影响种族/少数民族人口，如西班牙裔和非洲裔美国人（AA）妇女。我们认为，怀孕会增强女性乳腺组织的BC发展，这些女性的乳腺组织容易受到怀孕的促进作用，通过未知的遗传和/或环境因素，这种脆弱性至少部分解释了在生育率较高的女性中观察到的EOBC风险增加和不良结局。本研究项目的直接目标是检查发生在短暂的高风险产后期的BC的表观遗传概况与在此期间以外诊断的BC。研究将在不列颠哥伦比亚西班牙裔妇女的病例系列中进行，这一人口的特点是产次高。我们的具体目标是：1）定义风险因素、肿瘤亚型和临床病理学特征，这些风险因素、肿瘤亚型和临床病理学特征与在西班牙裔妇女中相对于在该时期之外的那些风险增加的产后时期发生的BC相关; 2）检验以下假设：在风险增加的产后时期诊断的肿瘤中特异性蛋白质编码基因启动子的甲基化比在短暂高风险时期之外发生的肿瘤中更频繁;以及3）检验在产后诊断的肿瘤中miRNA基因更可能发生表观遗传学改变的假设。所提出的工作的结果可能进一步阐明在绝经前EOBC中发挥作用的可能机制，特别是那些与最近怀孕时间相关的机制。

DESCRIPTION (provided by applicant): Risk of breast cancer (BC) increases in the period immediately following pregnancy. BCs that occur in the post-partum period have more aggressive histopathological features, are more likely to metastasize, and are associated with worse patient outcomes. On average, they also affect younger women and may represent a substantial proportion of early onset breast cancer (EOBC), a phenomenon that disproportionately affects racial/ethnic minority populations, such as Hispanics and African American (AA) women. We propose that pregnancy enhances development of BC in women whose breast tissue is vulnerable to the promotional effects of pregnancy via as yet unknown genetic and/or environmental factors and that this vulnerability explains at least part of the increased risk of EOBC and poor outcomes observed in women with higher fertility. The immediate objective of this research project is to examine epigenetic profiles of BCs that occur in the transient high-risk post-partum period versus those diagnosed outside of this period. Studies will be conducted in BC case series of Hispanic women, a population characterized by high parity. Our specific aims are to: 1) Define the risk factors, tumor sub-types, and clinicopathological characteristics associated with BCs occurring in the post-partum period of increased risk relative to those outside this period in Hispanic women; 2) Test the hypothesis that methylation of specific protein-coding gene promoters is more frequent in tumors that are diagnosed in the post-partum period of increased risk vs. those occurring outside the transient high risk period; and, 3) Test the hypothesis that miRNA genes are more likely to be epigenetically altered in tumors diagnosed in the post-partum period. Results of the proposed work may further elucidate possible mechanisms that play a role in pre-menopausal EOBC, particularly those mechanisms that are temporally related to a recent pregnancy.