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

基本信息

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
项目类别：
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&apos 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

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&apos 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

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项目摘要

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）妇女比欧洲血统（EA）更有可能在45岁之前被诊断为乳腺癌，并且具有更侵略性的肿瘤，其特征是高级，雌激素和孕酮受体和Her-2负染色（三重阴性）。它们也更有可能患有基础样的乳腺肿瘤，这是一种固有的乳腺癌亚型，预后最差。这些差异的原因尚不清楚，现有研究缺乏研究年轻女性乳腺癌亚型危险因素的统计能力。在该计划项目中，我们将汇集来自卡罗来纳州乳腺癌研究（CBC），黑人妇女健康研究（BWHS），妇女卫生研究圈（WCHS）和多种族同伴（MEC）（MEC）的数据和样本，并继续累积5500多个案例和5500个对照的最终样本大小。我们将通过其内在亚型收集组织块并将其分类，并研究四个高度互动项目中亚型的特定遗传，生物学和流行病学风险因素。具体的目的是检查诊断年龄和乳腺癌亚型的年龄之间的关联和1）最近在GWAS发现中鉴定出的遗传基因座，使用细映射来鉴定潜在的因果等位基因； 2）怀孕史和哺乳，以及相关途径中遗传变异的潜在修饰； 3）体型，早期生活和成人体育锻炼以及基因/环境相互作用； 4）可能在非洲适应特有感染性疾病（稳健的免疫反应）和强烈的阳光（皮肤色素高）的危险因素，但西方社会可能导致过度炎症环境和维生素D缺乏症，这可能与早期，积极的乳腺癌有关。互动目的将研究亚型与遗传和生物学因素之间的关系，以及流行病学特征。支持所有项目的核心包括1）行政核心； 2）数据收集核心； 3）生物晶体核心； 4）生物统计学和数据管理核心。通过汇总我们的数据，标本，重要的是研究这些协同假设的专业知识，我们将阐明AA妇女中侵略性，早期发作乳腺癌的病因。