Breast Cancer Risk and Molecular Change After Chernobyl

切尔诺贝利事故后乳腺癌风险和分子变化

• 批准号: 8131679
• 负责人: SCOTT DAVIS
• 金额: $ 120.89万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-26 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8131679
• 关键词: Accidents; Address; Age; Alcohol consumption; Area; Belarus; Biological; Biological Assay; Birth; Blood specimen; Body mass index; Breast; Breast Cancer Risk Factor; Calendar; Case-Control Studies; Cells; Characteristics; Childhood Leukemia; Clinical; Communities; Country; DNA Repair; DNA Repair Gene; Defect; Diagnosis; Diagnostic; Dietary History; Dose; Dose-Rate; Environmental and Occupational Exposure; Epigenetic Process; Estrogen Receptors; Exercise; Exhibits; Exposure to; Family health status; Family history of; Female; Gene Amplification; Gene Silencing; Genes; Genomics; Genotype; Hormone Receptor; Hormones; Immunohistochemistry; Incidence; Individual; Induced Abortion; Ionizing radiation; Knowledge; Life; Loss of Heterozygosity; Low Dose Radiation; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of thyroid; Mammary Neoplasms; Medical History; Methods; Methylation; Molecular; Mutation; Pathology; Peer Review; Persons; Phenotype; Population; Pregnancy; Premenopause; Progesterone Receptor Status; Public Health; Publishing; Radiation; Radiation Accidents; Radiation induced damage; Radioactive Fallout; Radioisotopes; Recording of previous events; Recovery; Reporting; Reproductive History; Research Personnel; Resources; Review Literature; Risk; Risk Estimate; Risk Factors; Russia; Sampling; Shapes; Survivors; Therapeutic; Thyroid Gland; Time; Tissue Sample; Tumor Tissue; Ukraine; Uncertainty; Whole-Body Irradiation; Woman; cancer risk; case control; cohort; environmental radiation; experience; gene repair; insight; interest; irradiation; malignant breast neoplasm; neoplastic cell; novel strategies; population based; programs; radiation effect; residence; response

DESCRIPTION (provided by applicant): Exposure to ionizing radiation is well documented as a cause of breast cancer in women, but little is known about the effects on breast cancer risk of exposure to radiation at low doses, protracted over time, and the biologic mechanisms responsible for radiation associated breast cancer are poorly understood. Populations exposed to radiation from the Chernobyl accident provide a powerful and unique opportunity to investigate these questions. This study will capitalize on this opportunity and has two primary aims: 1) to investigate whether the risk of premenopausal breast cancer is associated with individual radiation dose to the breast from the Chernobyl accident, to estimate the risk per unit dose, to investigate the shape of the dose- response, and potential dose effect modifying factors, including molecular characteristics and established breast cancer risk factors; and 2) to investigate whether the association of breast cancer risk with radiation exposure differs according to characteristics of breast cancer, including hormone receptor status, genomic loss and gain, and specific alterations in 14 selected DMA repair genes. Premenopausal breast cancer cases diagnosed between 4/1/07 and 9/30/11 who were resident in the Bryansk Oblast of Russia at the time of the Chernobyl accident will be identified and their diagnosis confirmed by an independent panel of experts. Controls will be selected from female residents of the Bryansk Oblast without breast cancer and matched to cases by calendar year of birth and raion of residence on April 26, 1986. For all cases and controls the following will be collected: 1) demographic and personal and family health history; 2) residential and dietary history and 3) a blood sample. Individual radiation dose to the breast will be estimated for each case and control. Fresh breast tumor tissue will be collected for each case for pathology review, immunohistochemistry, and recovery of pure tumor cell samples, and DMA from these cell samples will be extracted for array studies, STR analysis and methylation assays. For cases DMA will be extracted and purified from tissue and blood samples to assess breast cancer characteristics, including hormone receptor status, loss of heterozygosity, gene amplification, and epigenetic gene inactivation, and to estimate the association between these characteristics and individual radiation dose. Gynecological, obstetrical, and clinical information will be collected from cases to assess the distribution of established risk factors for breast cancer in Russian women, including reproductive factors, family history of breast and/or ovarian cancer, hormone use, alcohol consumption, exercise, body mass index, and history of medical irradiation and to investigate their effect on the dose-response relationships assessed in Aims 1 and 2.

描述（由申请人提供）：暴露于电离辐射是女性乳腺癌的充分记录，但对乳腺癌对低剂量下辐射暴露的影响鲜为人知，随着时间的推移持续持久，以及导致辐射相关乳腺癌的生物学机制的影响很少。经历了切尔诺贝利事故辐射的人群为调查这些问题提供了一个强大而独特的机会。这项研究将利用这一机会，并具有两个主要目的：1）调查月球前乳腺癌的风险是否与切尔诺贝利事故中的乳房辐射剂量有关，以估计单位剂量的风险，以研究剂量反应的形状，以及潜在的剂量效应因素，包括分子特征和建立的乳腺癌风险因素； 2）研究乳腺癌风险与辐射暴露的关联是否取决于乳腺癌的特征，包括激素受体状态，基因组丧失和增益以及14个选定的DMA修复基因的特定改变。在切尔诺贝利事故发生时，将在4/1/07至9/30/11之间被诊断出在俄罗斯的Bryansk Opmast中被诊断出的绝经前乳腺癌病例，并确定其诊断由独立的专家小组确认。将从1986年4月26日出生年度和居住日期居住年份中，从不乳腺癌的情况下选择控制措施，并与案件相匹配。对于所有病例和控制，将收集以下内容：1）人口统计学和个人和家庭健康历史； 2）住宅和饮食史以及3）一个血液样本。将估计每种情况和对照的乳房辐射剂量。每种病例都将收集新鲜的乳腺肿瘤组织，以进行病理综述，免疫组织化学和纯肿瘤细胞样品的恢复，并将从这些细胞样品中提取DMA进行阵列研究，STR分析和甲基化测定。对于病例，将从组织和血液样本中提取并纯化DMA，以评估乳腺癌特征，包括激素受体状态，杂合性丧失，基因扩增和表观遗传基因失活，并估计这些特征和个体辐射剂量之间的关联。将从病例中收集妇科，产科和临床信息，以评估俄罗斯妇女乳腺癌既定的危险因素的分布，包括生殖因素，乳腺癌和/或卵巢癌的家族史，激素使用，饮酒，运动，体重指数以及医疗辐射的历史以及对剂量响应关系的影响，以评估其对剂量关系的影响。