Pregnancy Hormonal Profile/Biomarker Breast Cancer Risk

怀孕荷尔蒙概况/生物标志物乳腺癌风险

• 批准号: 6607154
• 负责人: Alan A. Arslan
• 金额: $ 4.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-03 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607154
• 关键词: African American; Asians; Hispanic Americans; age at pregnancy; alpha fetoprotein; biomarker; breast neoplasms; cancer prevention; cancer risk; caucasian American; cell differentiation; cell proliferation; chorionic gonadotropin; clinical research; cytoprotection; hormone regulation /control mechanism; human pregnant subject; immunologic assay /test; neoplasm /cancer epidemiology; neoplastic transformation; pregnancy; racial /ethnic difference; relaxin; statistics /biometry; women's health

DESCRIPTION (provided by applicant): A large body of epidemiological evidence indicates that an early first full-term pregnancy (before age 25) confers a lasting protection against breast cancer in the mother. Protection increases with decreasing age at pregnancy and is by and large independent of parity. Long-term protective effect of early full-term pregnancy could arise through pregnancy-related hormonal changes causing proliferation and full differentiation of mammary glandular epithelium in preparation for lactation. Fully differentiated mammary glandular cells are less susceptible to neoplastic transformation, while the vast majority of breast carcinomas arise from undifferentiated glandular cells. Experimental evidence revealed that specific hormones, such as human chorionic gonadotropin (hCG), relaxin (RLX) and alpha-fetoprotein (AFP), may play a role in breast tissue differentiation, and may be responsible for the protective effect of pregnancy on breast cancer risk. Recent data demonstrate that compared to Caucasian women in the US, Asian women had significantly higher second and third trimester levels of hormones affecting breast proliferation, such as estradiol (E2), estriol (E3), prolactin (PRL), and growth hormone (GH). These data support the hypothesis that women at low risk of breast cancer may have a specific hormonal profile during their pregnancies than women at high risk of breast cancer. We propose to expand these observations in a cross-sectional study by comparing pregnancy hormone levels affecting breast differentiation (hCG, RLX, AFP) and proliferation (E2, E3, PRL, GH) in women at high risk (Caucasian and African-American women in New York), intermediate risk (Latina immigrants in New York) and low risk (Asian immigrants in New York) of breast cancer. If the study hypothesis is confirmed, hormonal profile during pregnancy can be used for determination of a woman?s risk of breast cancer later in life. Moreover, specific hormone(s) or its analogues responsible for protective effect of pregnancy against breast cancer could be used for development of novel strategies for primary chemoprevention of breast cancer.

描述（由申请人提供）： 大量的流行病学证据表明， 足月妊娠（25岁之前）可提供持久的保护， 母亲患乳腺癌保护随着年龄的降低而增加， 怀孕，基本上不依赖于产次。长期保护性 早期足月妊娠的影响可能是通过妊娠相关的 激素变化引起乳腺增生和完全分化 为哺乳做准备的腺上皮。完全分化 乳腺细胞对肿瘤转化较不敏感， 虽然绝大多数乳腺癌起源于未分化的 腺细胞实验证据表明，特定的激素，如 如人绒毛膜促性腺激素（hCG）、松弛素（RLX）和甲胎蛋白 (AFP)，可能在乳腺组织分化中起作用，并且可能是 负责怀孕对乳腺癌风险的保护作用。 最近的数据表明，与美国的白人女性相比， 女性在妊娠中期和晚期的激素水平明显高于男性， 影响乳腺增生，如雌二醇（E2），雌三醇（E3）， 催乳素（PRL）和生长激素（GH）。这些数据支持这一假设 患乳腺癌风险较低的女性可能有特定的荷尔蒙特征， 在怀孕期间比乳腺癌高危女性更容易患乳腺癌。 我们建议在一项横断面研究中扩大这些观察结果， 比较影响乳腺分化的妊娠激素水平（hCG，RLX， AFP）和增殖（E2，E3，PRL，GH）在高风险的妇女（白人和 纽约的非洲裔美国妇女）、中等风险（ 纽约）和低风险（纽约的亚洲移民）的乳腺癌。如果 研究假设得到证实，可以使用怀孕期间的激素谱 一个女人的决心？在以后的生活中患乳腺癌的风险。此外，委员会认为， 负责保护作用的特定激素或其类似物 怀孕对乳腺癌的治疗可用于开发新的 乳腺癌的主要化学预防策略。