Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium

非裔美国女性乳腺癌亚型的流行病学：一个联盟

• 批准号: 8523798
• 负责人: Christine B. Ambrosone
• 金额: $ 351.2万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523798
• 关键词: 5q31; Address; Adult; Africa; African; African American; Age; Alleles; Behavioral; Biological; Biological Factors; Biology of Aging; Biometry; Body Size; Breast Cancer Epidemiology; Breast Cancer Model; Breast Cancer Risk Factor; Cause of Death; Cessation of life; Characteristics; Clinical; Collaborations; Communicable Diseases; Complex; Data; Data Collection; Development; Diagnosis; Disease; Disease Outcome; ERBB2 gene; Epidemiology; Estrogen Receptors; Estrogens; Etiology; European; Genetic; Genetic Markers; Goals; Health; Histopathologic Grade; Immune response; Incidence; Individual; Inflammatory; Lactation; Life; Malignant Neoplasms; Mammary Neoplasms; Maps; Meta-Analysis; Modeling; Modification; Negative Staining; Outcome; Pathway interactions; Penetrance; Physical activity; Predisposition; Pregnancy Histories; Prevention; Prevention program; Progesterone; Progesterone Receptors; Reproductive History; Research; Resources; Risk; Risk Factors; Sample Size; Sampling; Skin Pigmentation; Societies; Source; Specimen; Subgroup; Sunlight; Tissues; Tumor Biology; Tumor Subtype; Vitamin D Deficiency; Woman; Women' s Health; breast cancer diagnosis; cohort; data management; design; disorder subtype; early onset; gene environment interaction; genetic variant; genome wide association study; health disparity; lifestyle factors; malignant breast neoplasm; modifiable risk; novel; outcome forecast; programs; receptor; reproductive; therapeutic target; tumor; young woman

Women of African ancestry (AA) women are more likely than those with European ancestry (EA) to be diagnosed with breast cancer before age 45, and to have more aggressive tumors, characterized by high grade, with negative staining for estrogen and progesterone receptors and HER-2 (triple negative). They are also more likely to have basal-like breast tumors, an intrinsic breast cancer subtype with the poorest prognosis. The reasons for these disparities are unclear, and existing studies lack the statistical power to investigate risk factors for breast cancer subtypes among young women. In this Program Project, we will pool data and samples from the Carolina Breast Cancer Study (CBCS), the Black Women's Health Study (BWHS), the Women's Circle of Health Study (WCHS) and the Multi-ethnic Cohort (MEC) and continue to accrue cases for a final sample size of more than 5500 cases and 5500 controls. We will collect tissue blocks and classify cancers by their intrinsic subtypes, and investigate specific genetic, biologic and epidemiologic risk factors for subtypes in four highly interactive projects. The specific aims are to examine associations between age at diagnosis and breast cancer subtypes and 1) genetic loci identified in recent GWAS findings, using fine-mapping to identify potential causal alleles; 2) pregnancy history and lactation, and potential modification by genetic variants in related pathways; 3) body size, early life and adult physical activity, and gene/environment interactions; and 4) risk factors that may have been adaptive in Africa to endemic infectious disease (robust immune response) and intense sunlight (high skin pigmentation), but that in western society may result in hyper-inflammatory milieu and vitamin D deficiency, which may be related to early, aggressive breast cancer. Interactive aims will investigate relationships between subtypes and genetic and biologic factors, as well as epidemiologic characteristics. Cores that support all of the projects include the 1) Administrative Core; 2) Data Collection Core; 3) Biospecimen Core; and 4) Biostatistics and Data Management Core. By pooling our data, specimens, and importantly, expertise to investigate these synergist hypotheses, we will elucidate much of the etiology of aggressive, early onset breast cancers in AA women.

非洲血统 (AA) 女性比欧洲血统 (EA) 女性更有可能在 45 岁之前被诊断出患有乳腺癌，并且肿瘤更具侵袭性，其特点是恶性程度高，雌激素和孕激素受体以及 HER-2 呈阴性染色（三阴性）。他们也更有可能患有基底样乳腺肿瘤，这是一种预后最差的固有乳腺癌亚型。造成这些差异的原因尚不清楚，现有研究缺乏统计能力来调查年轻女性乳腺癌亚型的危险因素。在此计划项目中，我们将汇集来自卡罗莱纳州乳腺癌研究 (CBCS)、黑人女性健康研究 (BWHS)、女性健康圈研究 (WCHS) 和多种族队列 (MEC) 的数据和样本，并继续积累病例，最终样本量将超过 5500 例病例和 5500 例对照。我们将收集组织块并按其内在亚型对癌症进行分类，并在四个高度互动的项目中研究亚型的特定遗传、生物学和流行病学危险因素。具体目标是检查诊断年龄与乳腺癌亚型之间的关联，以及 1) 最近 GWAS 研究结果中确定的遗传位点，使用精细绘图来识别潜在的因果等位基因； 2) 妊娠史和哺乳史，以及相关途径中遗传变异的潜在修饰； 3) 体型、早期生命和成年体力活动以及基因/环境相互作用； 4）风险因素在非洲可能适应地方性传染病（强大的免疫反应）和强烈的阳光（高皮肤色素沉着），但在西方社会可能导致高炎症环境和维生素 D 缺乏，这可能与早期侵袭性乳腺癌有关。互动目标将调查亚型与遗传和生物因素以及流行病学特征之间的关系。支持所有项目的核心包括 1) 管理核心； 2）数据采集核心； 3) 生物样本核心； 4) 生物统计和数据管理核心。通过汇集我们的数据、样本以及重要的专业知识来研究这些协同剂假设，我们将阐明 AA 女性中侵袭性早发乳腺癌的大部分病因。