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Role of FSH in postmenopausal obesity and breast cancer

FSH 在绝经后肥胖和乳腺癌中的作用

基本信息

批准号：
10446232
负责人：
Jennifer Wright Bea
金额：
$ 80.73万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10446232
关键词：
Accounting Adipose tissue Age Ancillary Study Attention Automobile Driving Bilateral oophorectomy Binding Biological Markers Body Composition Body Weight Body fat Body mass index Breast Breast Cancer Prevention Breast Cancer Risk Factor Buffaloes Cancer Prevention Intervention Case-Control Studies Clinical Clinical Trials Computer software Conjugated Equine Estrogens Data Development Dual-Energy X-Ray Absorptiometry Estradiol Estrogen receptor positive Estrogens Ethnic Origin Feedback Follicle Stimulating Hormone Follicle Stimulating Hormone Receptor Future Goals Gonadotropin Releasing Hormone Inhibitor Goserelin Growth Factor Hormonal Hormones Human Hysterectomy Image Incidence Inflammatory Investigation Joints Leptin Malignant Neoplasms Malignant neoplasm of prostate Mammary Neoplasms Measures Mediating Mediator of activation protein Medroxyprogesterone 17-Acetate Menopause Modeling Obesity Observational Study Osteoporosis Ovarian Participant Pharmaceutical Preparations Pilot Projects Postmenopause Pre-Clinical Model Premenopause Prevention Preventive therapy Process Race Randomized Reporting Resources Risk Factors Role Safety Sampling Scanning Serum Source Testing Therapeutic Therapy trial Time Tissue Banks Translations Visceral Woman Women&apos s Health adjudicate arm base bone breast cancer diagnosis breast tumorigenesis cancer subtypes case control cohort design druggable target epidemiology study experience follow-up hormone therapy improved innovation insight interest large datasets malignant breast neoplasm novel obesity development phase 3 testing pre-clinical receptor research clinical testing subcutaneous waist circumference

项目摘要

ABSTRACT There is strong and consistent evidence for an association between obesity and post-menopausal breast cancer; however, the exact mechanisms are not clear. Follicle stimulating hormone (FSH) increases with menopause, concomitant with increased adiposity, particularly visceral adipose tissue (VAT). Recent preclinical data suggests that FSH may drive the deleterious shift in adiposity, independent of estrogen (E2). Further, FSH receptors are now known to be expressed in breast tumors. To date, there have been no large- scale human investigations of these FSH-adiposity-breast cancer associations. Using the Women's Health Initiative (WHI), a long-term national epidemiologic study of postmenopausal women, we will test the hypothesis that FSH drives adiposity postmenopausally, both cross-sectionally and longitudinally. Large subsets of WHI participants completed repeat dual energy x-ray absorptiometry (DXA) scans, and therefore have available robust measures of adiposity (including a novel measure of VAT) and banked serum from the randomized hormone therapy trials (N=1400) and the observational study (OS; N=1499). Second, using a case-control design, we will test the hypothesis that higher baseline FSH levels associate with increased risk of breast cancer using adjudicated cancer incidence data spanning >25 years follow-up (N=785 cases; N=2510 non-cases). Further, we will determine whether adiposity mediates the FSH-breast cancer risk associations. For all analyses, we will account for exogenous HT use (conjugated equine estrogen ± medroxyprogesterone acetate or reported HT use in the OS), endogenous estrogen (E2), and adipose-derived hormones that directly or indirectly regulate FSH (e.g. leptin). Our study is the first comprehensive epidemiologic investigation of FSH and obesity to measure and study FSH levels in the years prior to breast cancer diagnosis to assess the potential role of FSH in breast cancer. This study, which includes rich hormone and body composition data will enable immediate translation to more precise breast cancer prevention interventions aligned with new medications in the pipeline or currently in use for other cancers and osteoporosis, such as FSH and FSH receptor modulators, upstream GnRH antagonists (e.g. goserelin), and estetrol (E4).

摘要