Epigenetic Modifiers of Breast Cancer Risk

乳腺癌风险的表观遗传因素

• 批准号: 6802845
• 负责人: THERESA SWIFT-SCANLAN
• 金额: $ 4.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2007-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802845
• 关键词: DNA methylation; brca gene; breast neoplasms; cancer risk; case history; chemical structure function; clinical research; disease /disorder etiology; family genetics; female; gene environment interaction; gene induction /repression; genetic regulation; genetic susceptibility; human subject; mammary epithelium; molecular oncology; molecular pathology; neoplasm /cancer genetics; nucleic acid quantitation /detection; nucleic acid structure; nursing research; patient oriented research; polymerase chain reaction; predoctoral investigator; tumor suppressor genes; women' s health

DESCRIPTION (provided by applicant): Breast cancer (BC) is a complex disease with both genetic and environmental causes, and is the second leading cause of cancer death in women. Most women who develop breast cancer (approximately 70%) have no known family history or obvious risk factors. The remaining 30% of cases tend to aggregate in families, and 5-7% of these are heritable through BRCA1 and BRCA2 mutations, the only gene tests currently available for breast cancer. Recent molecular studies of breast ductal epithelial cells and tumor tissue have demonstrated the presence of several DNA repair and tumor control genes whose expression into functional proteins is effectively shut down or silenced via DNA methylation. It is hypothesized that the presence of silenced tumor control genes in breast epithelial cells may presage the eventual development of BC in women with such molecular modifications. The specific aims of this research are: 1) to identify methylation suppressed tumor control genes in DNA isolated from breast tumor tissue and surrounding healthy breast tissue in a cohort of women at high risk for BC, as compared to a case-matched control cohort of women at average risk for BC, and 2) to determine the predictive contributions of family and personal factors on breast cancer outcome, such as a history of BC, age-of-onset, parity, age at menarche, previous breast biopsies, endogenous and exogenous hormone exposure, screening history, and BRCA mutation status. This research has implications for improving risk assessment, and may ultimately aid women in the decision-making process regarding screening and risk reduction prophylactic measures such as risk reduction mastectomy and chemoprevention.

描述（由申请人提供）：乳腺癌（BC）是一种复杂的疾病，既有遗传和环境原因，也是女性癌症死亡的第二大原因。大多数患乳腺癌的妇女（约70％）没有已知的家族史或明显的危险因素。其余30％的病例倾向于在家庭中汇总，其中5-7％可以通过BRCA1和BRCA2突变（目前可用于乳腺癌的唯一基因测试）遗传。最近对乳腺导管上皮细胞和肿瘤组织的分子研究表明，存在几种DNA修复和肿瘤控制基因，它们的表达在功能蛋白中被有效地关闭或通过DNA甲基化沉默。假设在乳腺上皮细胞中存在沉默的肿瘤控制基因的存在可能会预示具有这种分子修饰的女性中BC的最终发展。这项研究的具体目的是：1）鉴定甲基化抑制从乳腺肿瘤组织中分离出的DNA中的肿瘤控制基因，并围绕着健康的妇女群体中的健康乳腺组织，与BC平均风险的病例对照组相比，女性的妇女对照组的群体和个人伴侣的预测因素是对乳腺癌的预测因素，例如，诸如乳腺癌的预测因素，例如，诸如乳腺癌的预测因素，例如，bc的病例对照组相比，例如，在乳腺癌中造成了预测贡献。初潮，以前的乳房活检，内源性和外源激素暴露，筛查病史和BRCA突变状态。这项研究对改善风险评估具有影响，最终可能会帮助妇女参与筛查和降低风险降低预防性措施（例如降低风险乳房切除术和化学预防）的决策过程。