Estrogen Metabolites, Related Genes and Breast Cancer

雌激素代谢物、相关基因与乳腺癌

基本信息

批准号：
7233207
负责人：
Anne Zeleniuch-Jaquotte
金额：
$ 92.02万
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 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7233207
关键词：
2-hydroxyestrone 4-OH-E(2)4-hydroxyestrone Abbreviations Address Affect Age Alleles Androgens Appendix Aromatic Hydrocarbons Attention Benign Beta-glucuronidase Binding Proteins Biological Blood Blood Circulation Blood specimen Body mass index CYP1B1 gene CYP3A4 gene CYP3A5 gene Carotenoids Cells Chlorinated Hydrocarbons Cohort Studies Collaborations Colorectal Confidence Intervals Cytochrome P450 DNA DNA Repair Gene Data Disease Endometrial Enzymes Estradiol Estrogen Metabolism Estrogen Receptors Estrogens Estrone Folate Follow-Up Studies Fostering Funding Genes Genetic Genetic Polymorphism Genetic Variation Genotype Grant Health Homocysteine Homocystine Hormones Hydroxyestrones Hydroxylation Institution Insulin-Like Growth Factor I Investigation Knowledge Lead Learning Life Style Liver Luteinizing Hormone Malignant Neoplasms Measures New York Numbers Odds Ratio Organ Ovarian Paper Pathway interactions Phase Phytoestrogens Play Publishing Range Rate Relative Risks Research Research Personnel Risk Factors Role Running Sampling Selection Bias Series Serum Source Specimen Sweden Tissues Uncertainty Universities Uridine Urine Variant Weight Woman Women&apos s Health base breast cancer diagnosis cancer risk cohort cost effective design enzyme activity experience follow-up genetic variant indexing malignant breast neoplasm programs size sulfation sulfotransferase

项目摘要

DESCRIPTION (provided by applicant): The NYU Women's Health Study (NYUWHS) cohort has played a leading role in elucidating the associations of estrogens and androgens with breast cancer, based on blood samples that were obtained prospectively in 1985-91 from over 14,000 healthy women of ages 35-65. We now team up with another cohort from the Northern Sweden Health and Disease Study in Umea to address questions about the roles of estrogen metabolites in breast cancer. The proposed grant period would extend the NYUWHS follow-up to about 19 years on average and would permit the accrual of nearly 1,000 incident breast cancer cases, while the Umea study will have over 600 cases. The follow-up and cancer case ascertainment rates have been high in both studies. The study will investigate how much levels of estrogen metabolites - which can be both estrogenic and genotoxic - affect breast cancer risk, and the degree to which functional polymorphisms in estrogen metabolism genes are predictive of estrogen metabolite levels and of breast cancer risk. We hypothesize that: Circulating levels of 16alpha-hydroxyestrone are positively associated with breast cancer risk, and the 2-hydroxyestrone to 16alpha-hydroxyestrone ratio is negatively associated with breast cancer; Genetic polymorphisms associated with altered activity of enzymes catalyzing 16alpha-hydroxylation (CYP3A4 and CYP3A5) and 4-hydroxylation (CYP1B1) are associated with breast cancer risk. Functional polymorphisms in the sulfotransferase and glucuronidase genes that diminish estrogen conjugation activity are associated with increased breast cancer risk. Over the last five years, the NYUWHS cohort has been the basis for investigations, with a series of collaborators, of numerous risk factors for various cancers (breast, colorectal, endometrial, ovarian) e.g., IGF-I and its binding proteins; organochlorines; serum carotenoids, phytoestrogens, folate and homocysteine; polymorphisms in luteinizing hormone and DNA repair genes. The availability of serum specimens, DNA, and lifestyle and dietary data collected prospectively, combined with the extended followup and increasing numbers of cancers, will allow the study to continue to foster the investigation of various biological risk factors for a range of cancers.

描述（由申请人提供）：纽约大学妇女健康研究（NYUWHS）同龄人在阐明雌激素和雄激素与乳腺癌的关联方面发挥了领先作用，基于1985 - 91年从14,000多名35-65岁的健康妇女中获得的血液样本。现在，我们与UMEA北部瑞典健康与疾病研究的另一个队列合作，解决了有关雌激素代谢产物在乳腺癌中的作用的问题。拟议的赠款期将平均将NYUWH的随访扩大到大约19年，并允许近1,000例事件乳腺癌病例的应计，而UMEA研究将有600多例。两项研究中的随访和癌症病例确定率都很高。该研究将研究雌激素代谢产物的水平水平既可以影响雌激素又可能影响乳腺癌的风险，以及雌激素代谢基因中功能多态性的程度可预测雌激素代谢物水平以及乳腺癌的风险。我们假设：16Alpha-Hydroxyestrone的循环水平与乳腺癌风险呈正相关，并且2-羟基链酮与16Alpha-Hydroxyestrone的比例与乳腺癌负相关。与催化16Alpha-羟基化（CYP3A4和CYP3A5）和4-羟基化（CYP1B1）催化酶的活性改变有关的遗传多态性与乳腺癌风险有关。硫代转移酶和葡萄糖醛酸酶基因的功能性多态性减少了雌激素结合活性与乳腺癌风险增加有关。在过去的五年中，NYUWHS队列一直是调查的基础，以及一系列合作者，为各种癌症（乳腺癌，结肠直肠，子宫内膜，卵巢，卵巢）提供了许多危险因素，例如IGF-I及其结合蛋白；有机氯；血清类胡萝卜素，植物雌激素，叶酸和同型半胱氨酸；黄体生成激素和DNA修复基因中的多态性。前瞻性收集的血清标本，DNA和生活方式以及饮食数据的可用性，以及癌症的扩展随访和越来越多的癌症，将使该研究能够继续促进对各种癌症的各种生物学风险因素的研究。