Epigenetic Modifiers of Breast Cancer Risk

乳腺癌风险的表观遗传因素

• 批准号: 7119697
• 负责人: THERESA SWIFT-SCANLAN
• 金额: $ 3.53万
• 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 2007-05-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119697
• 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）是一种具有遗传和环境原因的复杂疾病，是女性癌症死亡的第二大原因。大多数患乳腺癌的女性（约 70%）没有已知的家族史或明显的危险因素。其余 30% 的病例往往聚集在家庭中，其中 5-7% 的病例可通过 BRCA1 和 BRCA2 突变遗传，这是目前唯一可用于乳腺癌的基因检测。最近对乳腺导管上皮细胞和肿瘤组织的分子研究表明，存在多种 DNA 修复和肿瘤控制基因，这些基因的功能蛋白表达可通过 DNA 甲基化有效关闭或沉默。据推测，乳腺上皮细胞中沉默的肿瘤控制基因的存在可能预示着具有此类分子修饰的女性最终发展为乳腺癌。本研究的具体目的是：1) 与乳腺癌高危女性群体中的乳腺肿瘤组织和周围健康乳腺组织分离的 DNA 中鉴定甲基化抑制的肿瘤控制基因，并与病例匹配的对照群体进行比较。 BC 平均风险的女性，以及 2) 确定家庭和个人因素对乳腺癌结果的预测贡献，例如 BC 病史、发病年龄、产次、初潮年龄、既往乳腺活检、内源性和外源性激素暴露、筛查史和 BRCA 突变状态。这项研究对于改善风险评估具有重要意义，并可能最终帮助女性做出有关筛查和降低风险预防措施（例如降低风险乳房切除术和化学预防）的决策过程。