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: 7462278
• 负责人: Paolo G. Toniolo
• 金额: $ 38.95万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7462278
• 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）：在生命早期发生的第一次足月妊娠可以为母亲提供终身有效的乳腺癌保护。这种保护的原因尚不清楚，但许多啮齿类动物的实验观察表明，怀孕期间特定循环激素的长期升高在乳腺增殖和分化中发挥着重要作用，并减少了致癌损伤的影响。在一项病例对照研究（1890 例病例，3780 名对照）中，芬兰和瑞典的两个大型队列总共超过 120 万名受试者，我们将探讨在初产时获得的储存样本中测量的一组内源激素循环浓度之间的假定关联。 - 足月妊娠以及母亲随后发生乳腺癌。北欧国家为此类研究提供了独特的环境，因为它们拥有大量集中的产妇队列，并且可以访问高质量的全国数据库网络，包括癌症、人口和出生登记，通过这些数据库可以获取开展研究所需的大部分信息。将获得拟议的研究。 具体目标如下： 1) 扩展我们对妊娠早期慢性促性腺激素 (hCG) 保护作用的初步观察。我们假设，当年轻时怀孕时，hCG 的保护作用最大，并且随着怀孕年龄的增加，保护作用会减弱。将根据妊娠献血时的年龄定义三组病例和对照进行研究：<25 岁、25-29 岁和 30-39 岁 2) 确定与 hCG 假设类似的关联是否也适用于类固醇激素，正如实验文献所表明的那样。我们将测量雌二醇、孕酮、睾酮和性激素结合球蛋白 (SHBG)。 通过这项拟议的研究，我们试图揭示年轻时经历的第一次足月妊娠终身预防乳腺癌的生物学基础——这是乳腺癌流行病学中最著名的保护协会之一。对这种保护作用的更好理解将扩大我们对乳腺癌的理解，并可能为设计和测试新的预防策略开辟新的可能性，包括基于模仿妊娠保护作用的能力的化学预防。

项目成果

IGF-I during primiparous pregnancy and maternal risk of breast cancer.

• DOI: 10.1007/s10549-009-0519-6
• 发表时间: 2010-05
• 期刊: BREAST CANCER RESEARCH AND TREATMENT
• 影响因子: 3.8
• 作者: Chen, Tianhui;Lukanova, Annekatrin;Grankvist, Kjell;Zeleniuch-Jacquotte, Anne;Wulff, Marianne;Johansson, Robert;Schock, Helena;Lenner, Per;Hallmans, Goran;Wadell, Goran;Toniolo, Paolo;Lundin, Eva
• 通讯作者: Lundin, Eva

Early pregnancy sex steroids and maternal breast cancer: a nested case-control study.

早孕性类固醇和孕产妇乳腺癌：一项巢式病例对照研究。

• DOI: 10.1158/0008-5472.can-14-2150
• 发表时间: 2014
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Fortner,RenéeT;Schock,Helena;Kaaks,Rudolf;Lehtinen,Matti;Pukkala,Eero;Lakso,Hans-Åke;Tanner,Minna;Kallio,Raija;Joensuu,Heikki;Grankvist,Kjell;Zeleniuch-Jacquotte,Anne;Toniolo,Paolo;Lundin,Eva;Surcel,Helja-Marja
• 通讯作者: Surcel,Helja-Marja

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

妊娠期循环胰岛素样生长因子-I 和孕产妇患乳腺癌的风险。

• DOI: 10.1158/1055-9965.epi-11-0441
• 发表时间: 2011
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Toriola,AdetunjiT;Lundin,Eva;Schock,Helena;Grankvist,Kjell;Pukkala,Eero;Chen,Tianhui;Zeleniuch-Jacquotte,Anne;Toniolo,Paolo;Lehtinen,Matti;Surcel,Helja-Marja;Lukanova,Annekatrin
• 通讯作者: Lukanova,Annekatrin

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer.

• DOI: 10.1002/ijc.26070
• 发表时间: 2012-02-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Lukanova, Annekatrin;Surcel, Helja-Marja;Lundin, Eva;Kaasila, Marjo;Lakso, Hans-Ake;Schock, Helena;Husing, Anika;Kaaks, Rudolf;Koskela, Pentti;Grankvist, Kjell;Pukkala, Eero;Zeleniuch-Jacquotte, Anne;Lehtinen, Matti;Toniolo, Paolo
• 通讯作者: Toniolo, Paolo

Free β-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer.

游离β-人绒毛膜促性腺激素、总人绒毛膜促性腺激素和孕产妇患乳腺癌的风险。

• DOI: 10.2217/fon.13.208
• 发表时间: 2014
• 期刊: Future oncology (London, England)
• 作者: Toriola,AdetunjiT;Tolockiene,Egle;Schock,Helena;Surcel,Helja-Marja;Zeleniuch-Jacquotte,Anne;Wadell,Goran;Toniolo,Paolo;Lundin,Eva;Grankvist,Kjell;Lukanova,Annekatrin
• 通讯作者: Lukanova,Annekatrin