Hormonal effects on fallopian tube and ovary inclusion cysts, and ovarian cancer

激素对输卵管和卵巢包涵囊肿以及卵巢癌的影响

• 批准号: 8757947
• 负责人: NOAH D KAUFF
• 金额: $ 22.87万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8757947
• 关键词: Accounting; Affect; Age; Appearance; BRCA1 gene; Bilateral; Biology; Body mass index; Cancer Etiology; Cell Proliferation; Cells; Cessation of life; Chemoprevention; Child; Clear Cell; Contraceptive Usage; Diagnosis; Disease; Epidemiologic Studies; Epithelial cyst; Epithelial ovarian cancer; Epithelium; Estradiol; Estrogen Receptors; Estrogen Therapy; Estrogens; Etiology; Exposure to; Foundations; Goals; Hormonal; Hormones; Lesion; Light; Luteal Phase; Malignant neoplasm of ovary; Mammalian Oviducts; Menopause; Menstrual cycle; Metaplastic; Mucinous; Mucinous Neoplasm; Mutation; Oral Contraceptives; Ovarian; Ovarian Carcinoma; Ovary; Ovulation; Phenotype; Population; Postmenopause; Pregnancy; Premenopause; Prevention strategy; Progesterone; Progesterone Receptors; Progestins; Proliferating; Reproductive History; Risk; Salpingo-Oophorectomy; Secondary to; Serous; Site; Source; Staging; Surface; Time; Tissues; Weight; Woman; base; cancer risk; disorder prevention; driving force; experience; fimbria; gastrointestinal; high risk; improved; interest; neoplastic; parity; pill; proliferative phase Menstrual cycle; protective effect; public health relevance; reproductive; screening

DESCRIPTION (provided by applicant): It is estimated that there will have been ~22,300 new diagnoses and ~15,500 deaths from ovarian cancer in the US in 2012. Five-year survival is less than 50%; there is currently no effective screening approach. Preventive strategies are of paramount importance. Increasing parity and increasing use of oral contraceptives (OCs) provide significant protection against ovarian cancer, as does an early age at menopause. The protective effects of parity and OC use continue for extended periods of time; epidemiological studies show that the parity effect lasts for at least 40 years, while the OC effect continues for t least 30 years after stopping OC use. The mechanism(s) underlying these effects are not understood. A long-favored hypothesis is that protection from parity and OC use is achieved by blocking ovulation, but recent evidence suggests that it may be by reducing exposure of the relevant tissue to 'unopposed' estrogen, i.e., estrogen that is not 'opposed' by a progestin. Pregnancy is associated with high levels of estrogen but also high levels of progesterone, while the estrogen in OCs is associated in each pill with a progestin and the extent of this is greater than during a normal menstrual cycle. Early menopause is protective as it reduces exposure of the relevant tissue to the relatively high levels of estrogen in the premenopausal period. It has recently become clear that the majority of high-grade serous ovarian cancers (HGSOC), which comprises some 70% of ovarian cancers, are likely to arise in the fallopian tube fimbria (FTF). Some HGSOCs also probably arise in cortical inclusion cysts (CICs) within the ovary. We propose that a major source of the protection from parity and OC use is due to their significantly reducing cell proliferation in FTF and CICs. Proliferating cell populations are more susceptible to carcinogenic effects secondary to increased chances of mutation and progression. There is some evidence that FTF proliferation is much greater in the follicular phase of the menstrual cycle ('unopposed' estrogen) than in the luteal phase ('opposed' estrogen). No information is available concerning proliferation in the postmenopausal period. Whether such changes occur in CICs is not known. We are proposing to determine proliferation rates in the FTF and CICs in the follicular and luteal phase of the menstrual cycle and after menopause in women undergoing a risk-reducing bilateral salpingo-oophorectomy (RR-BSO). The results of this study will provide valuable information for further hormonal chemoprevention efforts.

描述（由申请人提供）：据估计，2012年，美国卵巢癌的新诊断约为22,300次，约有15,500例死亡。五年生存率少于50％；目前没有有效的筛选方法。预防策略至关重要。奇偶校验和口服避孕药的使用日益增加，对卵巢癌提供了重大保护，更年期时代也是如此。平价和OC使用的保护作用持续了很长时间；流行病学研究表明，平均效应持续至少40年，而OC效应在停止使用OC后至少30年持续了30年。这些作用的基础机制尚不清楚。一个长期以来的假设是，通过阻止排卵来保护免受平价和OC的保护，但最近的证据表明，这可能是通过减少相关组织暴露于“无反抗的”雌激素的暴露，即孕激素不是“反对”的雌激素。妊娠与高水平的雌激素有关，但也与高水平的孕激素有关，而OCS中的雌激素与孕激素有关，其程度大于正常的月经周期。更年期是保护性的，因为它可以在绝经前时期将相关组织的暴露到相对较高的雌激素水平。最近，很明显，大多数高级浆液卵巢癌（HGSOC）可能会在输卵管纤维膜（FTF）中出现约70％的卵巢癌。卵巢内的皮质包含囊肿（CICS）可能还会出现一些HGSOC。我们建议，保护奇偶校验和OC使用的主要来源是由于它们在FTF和CICS中的细胞增殖大大减少了。增殖的细胞群体更容易受到 致癌作用继发于突变和进展的机会增加。有证据表明，在月经周期的卵泡相（“无反对”雌激素）的卵泡相比在黄体期（“反对”雌激素）要大得多。在绝经后时期，没有有关扩散的信息。在CIC中是否发生这种变化尚不清楚。我们提议确定月经周期的卵泡和黄体阶段中FTF和CICS的增殖率，以及在接受降低风险的双侧salpingo-opopopopopopopopophorortomy（RR-BSO）的妇女中更年期后的增生率（RR-BSO）。这项研究的结果将为进一步的荷尔蒙化学预防工作提供宝贵的信息。