Vitamin D, Related Genes and Breast Cancer Risk

维生素 D、相关基因和乳腺癌风险

基本信息

批准号：
8081797
负责人：
Anne Zeleniuch-Jaquotte
金额：
$ 98.88万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-15 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8081797
关键词：
25-hydroxyvitamin D Abbreviations Affect Age Age-Years American Apoptosis Area Biological Biological Markers Blood Donations Breast Cancer Cell Breast Cancer Genetics Breast Cancer Prevention Breast Cancer Risk Factor Case-Control Studies Catabolism Cell Proliferation Characteristics Code Cohort Studies Collaborations Confidence Intervals Cytochrome P450 DNA Data Databases Development Diagnosis Diagnostic Disease Enzymes Epidemiologic Studies Estradiol Estrogen Receptor Status Estrogen Receptors Estrogens Estrone Ethnic Origin Foundations Funding Future GC gene Genes Genetic Genetic Variation Genotype Gonadal Steroid Hormones Grant Haplotypes Health Hydroxylation Incidence Intake Intestines Joints Maintenance Malignant Neoplasms Mammary Gland Parenchyma Mammary gland Measurement Measures Mediating Mediator of activation protein Menopausal Status Metabolism Nested Case-Control Study New York Pathway interactions Phenotype Play Population Postmenopause Production Prospective Studies Public Health Quality Control Questionnaires RXRA gene Race Receptor Activation Recommended Daily Allowances Recording of previous events Recruitment Activity Reproductive History Research Research Infrastructure Research Personnel Resources Retinoid X Receptor alpha Risk Risk Factors Role Sampling Screening procedure Selection Bias Serum Single Nucleotide Polymorphism Skin Study Subject Sweden Testing Time United States Universities Variant Vitamin D Vitamin D-Binding Protein Vitamin D3 Receptor Woman Women&apos s Health absorption cancer risk case control cohort cost effective design dietary supplements disorder risk follow-up gene function genetic variant genome wide association study improved interest malignant breast neoplasm prospective protective effect receptor repository reproductive tumor

项目摘要

DESCRIPTION (provided by investigator): A large body of experimental data indicates that vitamin D inhibits cellular proliferation and induces differentiation and apoptosis, suggesting a protective effect against cancer. The enzymes coding for the formation and degradation of 1,25(OH)2D, the active metabolite of vitamin D, are present in both normal and cancer breast cells, as is the vitamin D receptor, a key mediator in the vitamin D pathway. Ecological and case- control studies support a protective role of vitamin D against breast cancer; however, prospective data are sparse. Moreover, few studies have measured circulating 25(OH)D which is considered the best indicator of vitamin D status because it captures both the absorption of vitamin D in the intestine and its production in the skin. We propose to conduct a comprehensive study of the vitamin D pathway in relation to breast cancer risk. Because vitamin D impacts cell proliferation, the main mechanism by which estrogens increase breast cancer risk, we will also assess whether vitamin D modifies the association of circulating estradiol with breast cancer risk in postmenopausal women. The study will be a case-control study nested within two cohorts, the NYU Women's Health Study and the Mammary Screening Cohort in Sweden. These two cohorts have a similar design and collected biological samples prospectively. A total of 1,995 incident cases is expected to be observed within these two cohorts. One (or two for cases d 52 years of age) control(s) will be selected for each case, matching the case on cohort, race/ethnicity, menopausal status, age at, and date of, blood donation. In addition to baseline measurements, we will assess 25(OH)D at repeat points in time in about 50 percent of the matched sets (2 samples in 25 percent and 3 samples in 25 percent). We will also assess genetic variation in vitamin D-related genes (CYP27A1, CYP24A1, DBP, VDR, and RXRA) and evaluate the joint effects of circulating 25(OH)D and variants in these genes on breast cancer risk. Circulating levels of estradiol will be measured in postmenopausal matched sets. PUBLIC HEALTH RELEVANCE: Breast cancer is the cancer with highest incidence in women in the US. Most of the known risk factors for breast cancer (genetic and reproductive) are not readily modifiable. By contrast, if vitamin D proves to be protective against breast cancer, levels are readily modifiable through supplements which are nontoxic and inexpensive. Since a significant fraction of the American population has suboptimal levels of vitamin D, there would be a large potential for breast cancer prevention.

描述（研究人员提供）：大量实验数据表明，维生素D抑制细胞增殖并诱导分化和凋亡，表明针对癌症具有保护作用。编码编码为1,25（OH）2d的形成和降解的酶，即维生素D的活性代谢产物，在正常和癌症乳腺细胞中都存在，维生素D受体也是维生素D受体，这是维生素D途径中的关键介体。生态和病例控制研究支持维生素D对乳腺癌的保护作用；但是，前瞻性数据很少。此外，很少有研究测量25（OH）D的循环，这被认为是维生素D状态的最佳指标，因为它既捕获了肠道中维生素D的吸收及其在皮肤中的产生。我们建议对维生素D途径进行有关乳腺癌风险的全面研究。由于维生素D会影响细胞增殖，这是雌激素增加乳腺癌风险的主要机制，我们还将评估维生素D是否会修饰循环雌二醇与绝经后妇女中乳腺癌风险的关联。该研究将是一项嵌套在两个队列中的病例对照研究，纽约大学妇女健康研究和瑞典的乳腺筛查队列。这两个队列具有相似的设计，并预期收集了生物样品。预计在这两个队列中将总共观察到1,995例事件。每种情况下，将选择一个（52岁的病例）控制，与队列，种族/民族，绝经状态，献血的年龄和日期相匹配。除了基线测量值外，我们还将在大约50％的匹配集（25％的25％样本和25％的3个样本中评估25（oh）d。我们还将评估维生素D相关基因（CYP27A1，CYP24A1，DBP，VDR和RXRA）的遗传变异，并评估这些基因对乳腺癌风险的循环25（OH）D的关节作用。雌二醇的循环水平将在绝经后匹配的集合中测量。公共卫生相关性：乳腺癌是美国女性发病率最高的癌症。大多数已知的乳腺癌危险因素（遗传和生殖）不容易修改。相比之下，如果维生素D被证明是针对乳腺癌的保护性，则可以通过无毒且廉价的补充剂来修改水平。由于大部分美国人群的维生素D水平次优，因此预防乳腺癌的可能性很大。