A Pooled Analysis to Identify New Ovarian Cancer Risk Factors

确定新的卵巢癌危险因素的汇总分析

• 批准号: 7663022
• 负责人: CELESTE Leigh PEARCE
• 金额: $ 35.05万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7663022
• 关键词: Address; Attention; Cancer Etiology; Cessation of life; Characteristics; Contraceptive Usage; Data; Diagnosis; Disease; Dose; Epithelial ovarian cancer; Estrogen Therapy; Estrogens; Etiology; Exogenous Hormone Therapy; Exposure to; Histology; Hormones; Hysterectomy; Individual; Infertility; Light; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Menopause; Meta-Analysis; Modification; Obesity; Oral Contraceptives; Outcome; Ovulation; Pregnancy; Progesterone; Progestin Therapy; Progestins; Property; Recording of previous events; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Schedule; Stage at Diagnosis; Staging; Time; Treatment Protocols; Tumor Subtype; Woman; Work; base; cancer risk; cost; endometriosis; follow-up; hormone therapy; improved; interest; international center; member; public health relevance; tumor

DESCRIPTION (provided by applicant): Ovarian cancer is the eighth most common cancer in women, the fifth most common cause of cancer-related death in women and the leading cause of gynecological cancer death. One- and five-year survival is only 76% and 45%, respectively, primarily due to the late stage at diagnosis for most women. While it is clear that exogenous hormones in the form of oral contraceptives (OCs) are associated with decreased risk of epithelial ovarian cancer (ovarian cancer), the situation with the other major form of exogenous hormone use, namely, menopausal hormone therapy (HT) is less clear. We have recently shown that while duration of estrogen therapy (ET) use is clearly associated with increased risk of ovarian cancer, estrogen plus progestin therapy (EPT) is associated with a statistically significant lower risk than ET. This observation brings to light fundamental questions with regard to the etiology of ovarian cancer: If a progestin can ameliorate some of the risk-inducing properties of estrogen, what effect does a larger progestin dose have and does dose scheduling matter? And, if it is true that progestins can block the effect of estrogen on ovarian cancer risk it might suggest that the mechanism through which both OCs and pregnancy, both of which create higher than normal exposure to progestins, decrease risk is not through blocking ovulation, but rather through the increased progestin exposure. Also relevant is whether these effects differ based on histological subtype of the tumor, recency of use, or presence of other risk factors such as obesity. These questions need to be answered. In addition to HT, there are several additional suspected/known risk factors which are in need of further follow-up: endometriosis, infertility and hysterectomy. The relationship between risk of ovarian cancer and specific parameters of these exposures (e.g., timing of endometriosis, reasons for infertility, timing of hysterectomy), environmental modifiers of the association (e.g., history of OC use), and tumor characteristics needs to be addressed. Historically these would have been very difficult analyses to undertake because individual studies are not adequately powered, but members of the Ovarian Cancer Association Consortium (OCAC) have recognized the need to work collaboratively to pool data to address such questions. Fifteen groups from around the world have agreed to contribute data on more than 13,000 ovarian cancer cases and 17,000 healthy controls to comprehensively address the role of HT, endometriosis, infertility and hysterectomy with ovarian cancer risk in order to shed light on the etiology of the disease. Importantly, because the infrastructure of the OCAC has already been established and the investigators have a track record of working together this work can be conducted efficiently and cost-effectively. PUBLIC HEALTH RELEVANCE: Ovarian cancer is the eighth most common cancer in women, the fifth most common cause of cancer-related death in women and the leading cause of gynecological cancer death; one- and five-year survival is a paltry 76% and 45%, respectively. We will conduct pooled analyses of existing data using data from 15 groups from around on the world on more than 13,000 ovarian cancer cases and 17,000 healthy women to answer questions about risk of ovarian cancer and the following exposures of interest: menopausal hormone therapy, endometriosis, infertility and hysterectomy. Gaining a better understanding of ovarian cancer, which this project will provide, is critical to identifying women at risk and for improving the outcome for women who are diagnosed with this disease.

描述（由申请人提供）：卵巢癌是女性第八大常见癌症，女性癌症相关死亡第五大常见原因，也是妇科癌症死亡的主要原因。一年和五年生存率分别仅为 76% 和 45%，这主要是由于大多数女性诊断时已处于晚期。虽然口服避孕药（OC）形式的外源性激素显然与降低上皮性卵巢癌（卵巢癌）的风险相关，但另一种主要形式的外源性激素使用，即绝经期激素治疗（HT）的情况不太清楚。我们最近发现，虽然雌激素治疗 (ET) 的使用时间明显与卵巢癌风险增加相关，但雌激素加孕激素治疗 (EPT) 与 ET 相比，风险在统计学上显着降低。这一观察结果揭示了有关卵巢癌病因学的基本问题：如果孕激素可以改善雌激素的一些诱发风险的特性，那么较大的孕激素剂量会产生什么影响以及剂量安排是否重要？而且，如果孕激素确实可以阻止雌激素对卵巢癌风险的影响，那么可能表明口服避孕药和怀孕（两者都会产生高于正常水平的孕激素暴露）降低风险的机制并不是通过阻止排卵，而是通过增加孕激素暴露来实现。同样相关的是，这些影响是否因肿瘤的组织学亚型、使用的新近程度或肥胖等其他危险因素的存在而有所不同。这些问题需要得到解答。除了 HT 之外，还有一些其他可疑/已知的危险因素需要进一步随访：子宫内膜异位症、不孕症和子宫切除术。需要解决卵巢癌风险与这些暴露的具体参数（例如子宫内膜异位症的发生时间、不孕原因、子宫切除术的时间）​​、相关环境因素（例如口服避孕药的使用史）和肿瘤特征之间的关系。从历史上看，这些分析是非常困难的，因为个别研究的动力不足，但卵巢癌协会联盟 (OCAC) 的成员已经认识到需要合作汇集数据来解决这些问题。来自世界各地的 15 个组织已同意提供超过 13,000 例卵巢癌病例和 17,000 名健康对照者的数据，以全面探讨 HT、子宫内膜异位症、不孕症和子宫切除术与卵巢癌风险的关系，从而阐明该疾病的病因学。重要的是，由于 OCAC 的基础设施已经建立，并且调查人员拥有合作记录，因此这项工作可以高效且经济高效地进行。 公共卫生相关性：卵巢癌是女性第八大最常见癌症，是女性癌症相关死亡的第五大常见原因，也是妇科癌症死亡的主要原因；一年和五年生存率分别仅为 76% 和 45%。我们将使用来自世界各地 15 个团体的超过 13,000 例卵巢癌病例和 17,000 名健康女性的数据对现有数据进行汇总分析，以回答有关卵巢癌风险和以下感兴趣暴露的问题：更年期激素治疗、子宫内膜异位症、不孕症和子宫切除术。该项目将更好地了解卵巢癌，这对于识别处于危险中的女性以及改善被诊断患有这种疾病的女性的治疗结果至关重要。