Steroid Hormone Genes and Ovarian Cancer Risk

类固醇激素基因和卵巢癌风险

基本信息

批准号：
7821270
负责人：
MARY ANNE ROSSING
金额：
$ 46.43万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7821270
关键词：
Age Anabolism Androgens Awareness Behavioral Body Weight Breast Case-Control Studies Catabolism Cell division Characteristics Columbidae Contraceptive Usage Data Data Collection Development Diagnosis Disease Elements Enrollment Epidemiologic Studies Epidemiology Epithelial Cells Epithelial ovarian cancer Epithelium Estrogens Etiology Evaluation Exposure to Foundations Frequencies Funding Future Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals Gonadal Steroid Hormones Gonadotropins Growth Factor Haplotypes Hemorrhage Hormonal Hormone replacement therapy Hormones Inflammation Insulin-Like Growth Factor I Interview Investigation Knowledge Lead Life Link Malignant neoplasm of ovary Malignant neoplasm of prostate Measurement Measures Modeling Oral Contraceptives Ovarian Ovarian Stimulations Ovary Ovulation Pathway interactions Population Population Study Postmenopause Predisposition Prevention strategy Progesterone Progestins Regimen Relative (related person)Research Resources Risk Role Specimen Stimulus Variant Washington Waxes Woman aged base cancer epidemiology cancer risk carcinogenesis case control cohort gene function genetic analysis improved ovarian cancer prevention parity population based prevent response sample collection steroid hormone

项目摘要

DESCRIPTION (provided by applicant): Among the various models of ovarian carcinogenesis that have been put forth, hormonal influences predominate. An important current challenge in ovarian cancer epidemiology is to better understand the role of ovarian stimulation by progestogens, estrogens, and androgens in the etiology of this disease. Studies of variation in genes involved in hormonal pathways may contribute importantly in this regard, as they may (perhaps in combination with interview-based measurements of hormonal exposures) provide an improved assessment of the extent of ovarian exposure to particular hormones throughout life. We propose to use haplotype tagging SNPs and putative functional SNPs to examine the effect of variation in genes involved in the biosynthesis or catabolism of, or response to, progestogens, estrogens, and androgens on risk of ovarian cancer. We hypothesize that gene variants related to (1) reduced progestogen stimulation or (2) increased estrogen or androgen stimulation of the ovarian epithelium will be associated with increased risk. Developing a large, well-defined, population-based resource is an important element of this application. The proposed study builds on our ongoing population-based case-control study of ovarian cancer in western Washington State that includes women aged 35-74 years who are diagnosed with epithelial ovarian cancer from 2002-2005. Through this application, we will extend case and control interviewing and specimen collection for an additional three years (2006-2008) to enroll a study population of 1120 women with invasive epithelial ovarian cancer and 1760 controls. In addition to the proposed research on hormonal pathways, the collected specimens and data will provide a foundation for planned future studies of additional genes and pathways relevant to other models of ovarian carcinogenesis. Progress towards prevention of ovarian cancer is hindered by an inadequate understanding of the protective or causative mechanisms through which various exposures exert their effects. The proposed study, by expanding our knowledge of the role of progestogens, estrogens, and androgens in the development of ovarian cancer, will inform efforts to develop effective strategies to prevent this disease.

描述（由申请人提供）：在已经提出的各种卵巢癌发生模型中，激素影响占主导地位。当前卵巢癌流行病学的一个重要挑战是更好地了解孕激素、雌激素和雄激素对卵巢的刺激在该疾病的病因学中的作用。对涉及激素途径的基因变异的研究可能在这方面做出重要贡献，因为它们可能（也许与基于访谈的激素暴露测量相结合）提供对一生中卵巢暴露于特定激素的程度的改进评估。我们建议使用单倍型标记 SNP 和推定的功能 SNP 来检查参与孕激素、雌激素和雄激素生物合成或分解代谢或响应的基因变异对卵巢癌风险的影响。我们假设与（1）孕激素刺激减少或（2）卵巢上皮雌激素或雄激素刺激增加相关的基因变异将与风险增加相关。开发一个大型的、定义明确的、基于人口的资源是该应用程序的一个重要元素。这项拟议的研究建立在我们正在进行的华盛顿州西部卵巢癌人群病例对照研究的基础上，该研究包括 2002 年至 2005 年被诊断患有上皮性卵巢癌的 35-74 岁女性。通过这个应用程序，我们将把病例和对照访谈以及样本收集再延长三年（2006-2008 年），以招募由 1120 名患有浸润性上皮性卵巢癌的女性和 1760 名对照者组成的研究人群。除了拟议的激素途径研究之外，收集的标本和数据将为计划的未来研究与其他卵巢癌发生模型相关的其他基因和途径奠定基础。由于对各种暴露发挥作用的保护或致病机制了解不足，阻碍了预防卵巢癌的进展。这项拟议的研究通过扩大我们对孕激素、雌激素和雄激素在卵巢癌发展中的作用的了解，将为制定有效策略来预防这种疾病提供信息。