Metabolic Syndrome and Epigenetic Markers of Breast Cancer in Nigerian Women

摘要 2009年，发展中国家占全球乳腺癌新发病例的45%，2012年占57%， 预计到2030年，这一比例将增至70%。尼日利亚经历了三倍的增长 1973年至2012年间乳腺癌的发病率，与所谓的 “富足病”包括肥胖、高血压和糖尿病，这是一系列生化异常。 构成代谢综合征(METS)。最近在美国和欧洲的研究表明， 蛋氨酸与乳腺癌风险呈正相关，这表明尼日利亚乳腺癌发病率的上升 可能是甲型肝炎发病率增加的生物学后果。尼日利亚人，曾被诊断出患有乳腺癌 与其他非洲裔女性类似，女性也更有可能出现在更年轻的年龄， 侵袭性的、激素受体阴性的肿瘤，与较高的死亡率相关。更高价格的原因 这些肿瘤类型在非洲裔妇女中的流行率尚不清楚。表观遗传变化，通过DNA 甲基化、组蛋白修饰和微小RNA变化是乳腺癌发生的关键方面， 并同时受到遗传背景和环境暴露的影响。多项美国研究表明 观察到非洲和非洲之间关键乳腺癌基因的DNA甲基化水平存在显著差异 美国人和白人，包括BRCA1和BRCA2，CYP1A1，H-ras-1和Cyclin D1。DNA甲基化 尼日利亚女性的关键乳腺癌基因水平从未被检测过，这可能是 了解乳腺癌表型的种族差异的关键。小种特异性表观遗传学的鉴定 模式可能被用作暴露之间的关联的中间标记，例如 甲硫氨酸与乳腺癌发病率，或作为临床治疗和治疗的预后标志 干预措施。使用新诊断的乳腺癌病例和年龄匹配的健康对照组的样本，这项研究 这项研究的目的是在尼日利亚全面考察蛋氨酸与乳腺癌之间的联系，并按不同的类型进行研究。在……里面 此外，我们计划确定乳腺癌肿瘤和乳腺癌之间基因组DNA甲基化的差异。 患有和不患有甲状旁腺激素的妇女的邻近正常组织。这些发现将为以下方面提供关键信息 蛋氨酸对尼日利亚乳腺癌的影响，并提高我们对特定表观遗传学的理解 尼日利亚女性乳腺癌发生的变化；这可能不同于表观遗传学变化 在环境暴露有显著差异的非裔美国女性中观察到。

ABSTRACT Developing countries accounted for 45% of new breast cancer cases globally in 2009, and 57% in 2012, with these proportions projected to increase to 70% by 2030. Nigeria has experienced a three-fold increase in breast cancer incidence between 1973 and 2012, coinciding with an increase in the prevalence of so-called `diseases of affluence' including obesity, hypertension, and diabetes, a cluster of biochemical abnormalities that constitute Metabolic Syndrome (MetS). Recent studies in the US and Europe have shown a consistent positive association between MetS and breast cancer risk, suggesting that rising breast cancer rates in Nigeria may be a biological consequence of increasing rates of MetS. Once diagnosed with breast cancer, Nigerian women, similar to other women of African descent, are also more likely to present at younger ages, with highly aggressive, hormone-receptor negative tumors, associated with higher mortality. The reason for a higher prevalence of these tumor types in women of African descent is unclear. Epigenetic changes, through DNA methylation, histone modification and micro RNA changes are critical aspects of breast cancer tumorigenesis, and are influenced by both genetic background and environmental exposures. Multiple US studies have observed significant differences in DNA methylation levels of critical breast cancer genes between African- Americans and whites, including BRCA1 and BRCA2, CYP1A1, H-ras-1, and Cyclin D1. DNA methylation levels in critical breast cancer genes among Nigerian women have never been examined, and this may be the key to understanding racial differences in breast cancer phenotypes. Identification of race-specific epigenetic patterns could potentially be used as an intermediary marker of the association between exposures such as MetS and breast cancer incidence, or as prognostic markers for clinical management and therapeutic interventions. Using a sample of newly diagnosed breast cancer cases and age-matched healthy controls, this study aims to examine the association between MetS and breast cancer overall, and by sub-type in Nigeria. In addition, we plan to identify genome-wide DNA methylation differences between breast cancer tumor and adjacent normal tissue among women with and without MetS. These findings will provide critical information on the influence of MetS on breast cancer in Nigeria, and improve our understanding of the specific epigenetic changes that occur with breast cancer in Nigerian women; this is likely to be different from epigenetic changes observed among African American women with significantly different environmental exposures.