Pregnancy Hormones and Risk of Maternal Breast Cancer

怀孕激素与母亲患乳腺癌的风险

• 批准号: 7229528
• 负责人: Paolo G. Toniolo
• 金额: $ 46万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7229528
• 关键词: Address; Age; Animals; Biological; Birth; Blood Circulation; Blood Donations; Blood specimen; Breast; Breast Cancer Epidemiology; Breast Carcinoma; Carcinogens; Case-Control Studies; Cell Proliferation; Chemoprevention; Chronic; Complement; Comprehension; Country; Data; Databases; Deltastab; Diagnosis; Elevation; Estradiol; Estrogens; Exposure to; Finland; First Pregnancy Trimester; Gonadal Steroid Hormones; Gonadotropins; Hormonal; Hormones; Human; Human Chorionic Gonadotropin; Incidence; Invasive; Life; Light; Literature; Malignant Neoplasms; Mammary gland; Maternal Age; Measures; Mothers; Personal Satisfaction; Play; Population; Pregnancy; Preparation; Prevention strategy; Progesterone; Proliferating; Purpose; Registries; Research; Resources; Risk; Rodent; Role; Sex Hormone-Binding Globulin; Specimen; Stimulus; Sweden; Testing; Testosterone; Time; Woman; base; cancer diagnosis; case control; cohort; experience; indexing; interest; lifetime risk; malignant breast neoplasm; neoplasm registry; novel; protective effect; research study; size; steroid hormone

DESCRIPTION (provided by applicant): First full-term pregnancies occurring early in life, afford the mother a substantial lifetime protection from breast cancer. The reasons for such protection are unknown, but many experimental observations in rodents suggest that the prolonged elevation in specific circulating hormones in pregnancy play a fundamental role in mammary proliferation and differentiation and reduce the effects of carcinogenic insults. In a case-control study (1890 cases, 3780 controls) nested within two large cohorts in Finland and Sweden totaling over 1.2 million subjects we will explore putative associations between circulating concentrations of a panel of endogenous hormones measured in stored specimens obtained during a primiparous full-term pregnancy and the subsequent occurrence of breast cancer in the mother. Nordic countries provide a unique setting for such a study because of the availability of large, centralized maternity cohorts and the access to a network of high quality nationwide databases, including cancer, population and birth registries, through which most of the information needed to carry out the proposed study will be obtained. Specific aims are the following: 1) To extend our preliminary observations on the protective role of first-trimester chronic gonadotropin (hCG). We hypothesize that the protection of hCG is maximal when the pregnancy occurs at young age and that the protection decreases with increasing age at pregnancy. Three groups of cases and controls will be studied defined on age at the pregnancy blood donation: <25 years, 25-29 years and 30-39 years 2) To determine whether or not associations similar to those hypothesized for hCG also apply to steroid hormones, as the experimental literature suggests. We will measure estradiol, progesterone, testosterone, and sex-hormone binding globulin (SHBG). With the proposed study we seek to cast light into the biological basis of the lifetime protection from breast cancer of a first full-term pregnancy experienced at young age-one of the best known protective associations in breast cancer epidemiology. A better understanding of such a protection will expand our comprehension of breast cancer and may open up new possibilities to devise and test novel preventive strategies, including chemoprevention, based on the ability to mimic the protective effect of pregnancy.

描述（由申请人提供）：第一届全月妊娠在生命的早期发生，为母亲提供了对乳腺癌的大量保护。这种保护的原因尚不清楚，但是啮齿动物的许多实验观察结果表明，妊娠中特定循环激素的延长升高在乳腺增殖和分化中起着基本作用，并减少了致癌性损伤的影响。在一项病例对照研究（1890例病例，3780个对照）中，嵌套在芬兰和瑞典的两个大同类群中，总计超过120万受试者，我们将探索在原始的全术完全怀孕期间获得的储存标本中循环量的内源性激素循环浓度之间的推定关联，并在后续的术语中出现了乳腺癌的癌症。北欧国家为这项研究提供了独特的环境，这是因为大型，集中的产妇同伙以及进入包括癌症，人口和出生注册机构在内的高质量全国数据库网络的访问，将获得大多数进行拟议研究所需的信息。 具体目的是：1）扩展我们对第一孕期慢性促性腺激素（HCG）的保护作用的初步观察。我们假设，当怀孕在年轻时发生时，HCG的保护是最大的，并且随着怀孕年龄的增加，保护的保护是最大的。将研究三组​​病例和对照组在怀孕血液捐赠时的年龄定义：<25岁，25-29岁和30 - 39年2），以确定与实验性文献所暗示的类固醇激素相似的关联是否类似于类固醇激素。我们将测量雌二醇，孕酮，睾丸激素和性激素结合球蛋白（SHBG）。 在拟议的研究中，我们试图将灯光投入到乳腺癌的生物学基础上，以防止乳腺癌在年轻的乳腺癌流行病学中最著名的保护性关联之一。更好地理解这种保护将扩大我们对乳腺癌的理解，并可能基于模仿怀孕的保护作用的能力来设计和测试包括化学预防的新型预防策略，包括化学预防。