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。产后发生的bc具有更具侵袭性的组织病理学特征，更容易转移，并与较差的患者预后相关。平均而言，它们也会影响年轻女性，并可能在早发性乳腺癌（EOBC）中占相当大的比例，这一现象不成比例地影响种族/少数民族人群，如西班牙裔和非洲裔美国人（AA）妇女。我们认为，由于未知的遗传和/或环境因素，乳房组织易受妊娠促进作用的妇女，妊娠可促进乳腺癌的发展，这种易变性至少部分解释了在生育能力较高的妇女中观察到的EOBC风险增加和预后不良的原因。本研究项目的直接目的是检查发生在短暂高危产后期的bc与在此期间之外诊断的bc的表观遗传谱。研究将在不列颠哥伦比亚省西班牙裔妇女的病例系列中进行，这是一个以高胎次为特征的人群。我们的具体目的是：1)确定西班牙裔妇女产后发生的相对于其他时期风险增加的bc相关的危险因素、肿瘤亚型和临床病理特征；2)检验特异性蛋白编码基因启动子甲基化在高危产后诊断的肿瘤中比在短暂高危期外诊断的肿瘤更频繁的假设；3)验证miRNA基因在产后诊断的肿瘤中更容易发生表观遗传改变的假设。本研究的结果可能会进一步阐明绝经前EOBC的可能机制，特别是那些与近期怀孕有关的机制。

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.