Metabolic Syndrome and Epigenetic Markers of Breast Cancer in Nigerian Women

尼日利亚女性乳腺癌的代谢综合征和表观遗传标志物

• 批准号: 9555400
• 负责人: Tomi F Akinyemiju
• 金额: $ 13.45万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-28 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9555400
• 关键词: Address; Africa; African; African American; Age; Alcohol consumption; Applications Grants; BRCA1 gene; BRCA2 gene; Biochemical; Biological; Blood; Blood Glucose; Blood specimen; Breast Cancer Patient; Breast Cancer Risk Factor; Breast Cancer gene; CYP1A1 gene; Cancer Prognosis; Case-Control Studies; Cause of Death; Clinical Management; Communicable Diseases; Controlled Study; Country; Cyclin D1; DNA; DNA Methylation; Data; Developing Countries; Diabetes Mellitus; Diagnosis; Disease; Economic Development; Employee Strikes; Environmental Exposure; Epidemic; Epidemiology; Epigenetic Process; Europe; Foundations; Freezing; Genes; Genetic; Goals; HRAS gene; Health Planning; High Density Lipoproteins; High Prevalence; Hormone Receptor; Hospitals; Hypertension; Incidence; International; Kidney Diseases; Laboratories; Lasers; Life Style; Link; Mammary Gland Parenchyma; Mentors; Metabolic syndrome; MicroRNAs; Molecular; Molecular Epidemiology; Newly Diagnosed; Nigeria; Nigerian; Normal tissue morphology; Obesity; Pathway interactions; Pattern; Phenotype; Population; Positioning Attribute; Prevalence; Prognostic Marker; Questionnaires; Race; Recruitment Activity; Research; Residual state; Risk Factors; Role; Sampling; Sampling Studies; Ships; Smoking; Therapeutic Intervention; Tissue Sample; Tissues; Training; Triglycerides; Tumor Suppression; Waist-Hip Ratio; Woman; Women' s Group; World Bank; breast cancer diagnosis; cancer risk; cancer subtypes; early onset; epigenetic marker; experience; genome-wide; global health; histone modification; improved; low and middle-income countries; malignant breast neoplasm; metabolic rate; methylation pattern; mortality; outcome forecast; racial difference; triple-negative invasive breast carcinoma; tumor; tumor DNA; tumorigenesis; urban area

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.

抽象的 2009 年全球新发乳腺癌病例中，发展中国家占 45%，2012 年占 57%， 预计到 2030 年，这一比例将增至 70%。尼日利亚的人口增长了三倍 1973 年至 2012 年间乳腺癌发病率与所谓的患病率增加同时发生 “富贵病”包括肥胖、高血压和糖尿病（一系列生化异常） 构成代谢综合症（MetS）。美国和欧洲最近的研究表明， MetS 与乳腺癌风险呈正相关，表明尼日利亚乳腺癌发病率不断上升 可能是 MetS 发生率增加的生物学结果。尼日利亚人一旦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较年轻的年龄， 侵袭性、激素受体阴性肿瘤，与较高的死亡率相关。较高的原因 这些肿瘤类型在非洲裔女性中的患病率尚不清楚。通过 DNA 发生表观遗传变化 甲基化、组蛋白修饰和微小RNA变化是乳腺癌肿瘤发生的关键方面， 并受到遗传背景和环境暴露的影响。美国多项研究表明 观察到非洲人之间关键乳腺癌基因的 DNA 甲基化水平存在显着差异 美国人和白人，包括 BRCA1 和 BRCA2、CYP1A1、H-ras-1 和 Cyclin D1。 DNA甲基化 尼日利亚妇女中关键乳腺癌基因的水平从未被检查过，这可能是 了解乳腺癌表型的种族差异的关键。种族特异性表观遗传鉴定 模式有可能用作暴露之间关联的中间标记，例如 MetS 和乳腺癌发病率，或作为临床管理和治疗的预后标志物 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样本，这 研究旨在从整体上以及尼日利亚的亚型中探讨 MetS 与乳腺癌之间的关联。在 此外，我们计划确定乳腺癌肿瘤和乳腺癌肿瘤之间的全基因组 DNA 甲基化差异。 患有和不患有 MetS 的女性的邻近正常组织。这些发现将提供重要信息 MetS 对尼日利亚乳腺癌的影响，并提高我们对特定表观遗传的了解 尼日利亚女性乳腺癌发生的变化；这可能与表观遗传变化不同 在环境暴露程度显着不同的非裔美国女性中观察到。