Epigenetic Features of Pregnancy-Associated Breast Cancer in Hispanic Women

描述(申请人提供)：乳腺癌(BC)的风险在怀孕后的一段时间内增加。发生在产后时期的BCS具有更具侵袭性的组织病理学特征，更有可能转移，并与较差的患者预后相关。平均而言，它们也影响年轻女性，并可能占早发性乳腺癌(EOBC)的相当大比例，这一现象对种族/少数民族人口，如西班牙裔和非裔美国人(AA)妇女造成了不成比例的影响。我们认为，怀孕通过未知的遗传和/或环境因素，对其乳腺组织易受怀孕的促进作用的妇女，促进了BC的发展，这种脆弱性至少解释了EOBC风险增加的部分原因，以及在生育力较高的妇女中观察到的不良结局。这项研究项目的直接目标是检查发生在产后短暂高危时期的BCS的表观遗传学特征与这一时期以外确诊的BCS的表观遗传学特征。研究将在不列颠哥伦比亚省的西班牙裔妇女案例系列中进行，拉美裔妇女是一个以高平等为特征的群体。我们的具体目标是：1)确定与发生在拉美裔妇女产后高风险时期相比的BCS相关的风险因素、肿瘤亚型和临床病理特征；2)测试假设，即特定蛋白编码基因启动子的甲基化在产后高风险时期比发生在短暂的高风险时期以外的肿瘤更频繁；以及3)测试在产后诊断的肿瘤中miRNA基因更有可能发生表观遗传改变的假设。拟议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.