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%，主要是由于大多数女性的诊断晚期。虽然很明显，口服避孕药（OC）形式的外源性激素与上皮性卵巢癌（卵巢癌）的风险降低有关，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）的使用时间与卵巢癌的风险增加明显相关，但雌激素加孕酮治疗（EPT）的风险在统计学上显著低于ET。这一观察结果揭示了卵巢癌病因学方面的基本问题：如果一种雌激素可以改善雌激素的一些风险诱导特性，那么更大剂量的雌激素会产生什么影响，剂量安排是否重要？而且，如果孕激素确实可以阻断雌激素对卵巢癌风险的影响，那么这可能表明，OC和妊娠两者都产生高于正常水平的孕激素暴露，降低风险的机制不是通过阻断排卵，而是通过增加卵巢激素暴露。同样相关的是，这些效应是否基于肿瘤的组织学亚型、使用的新近程度或其他风险因素（如肥胖）的存在而不同。这些问题需要得到解答。除了HT，还有几个额外的可疑/已知的风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。卵巢癌风险与这些暴露的特定参数之间的关系（例如，子宫内膜异位的时间、不孕的原因、子宫切除的时间），相关的环境调节剂（例如，OC使用史）和肿瘤特征需要解决。从历史上看，这些分析是非常困难的，因为个别研究没有足够的动力，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个团体已同意提供超过13，000例卵巢癌病例和17，000例健康对照的数据，以全面解决HT，子宫内膜异位症，不孕症和子宫切除术与卵巢癌风险的作用，以阐明疾病的病因。重要的是，由于海外廉政公署的基础设施已经建立，调查人员有合作的记录，这项工作可以有效和具有成本效益地进行。 公共卫生关系：卵巢癌是女性第八大常见癌症，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为微不足道的76%和45%。我们将对现有数据进行汇总分析，使用来自世界各地15个组的13，000多例卵巢癌病例和17，000名健康女性的数据，以回答有关卵巢癌风险和以下相关风险的问题：绝经激素治疗，子宫内膜异位症，不孕症和子宫切除术。更好地了解卵巢癌，这一项目将提供，是至关重要的，以确定妇女的风险和改善妇女谁被诊断患有这种疾病的结果。