Steroid Hormone Genes and Ovarian Cancer Risk

类固醇激素基因和卵巢癌风险

• 批准号: 7255522
• 负责人: MARY ANNE ROSSING
• 金额: $ 73.9万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255522
• 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; 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; Invasive; Investigation; Knowledge; Lead; Life; Link; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Measurement; Measures; Modeling; Oral; Ovarian; Ovarian Stimulations; Ovary; Ovulation; Pathway interactions; Population; Population Study; Postmenopause; Predisposition; Prevention strategy; Progesterone; Progestins; Relative (related person); Research; Resources; Risk; Role; Specimen; Stimulus; Thinking; Treatment Protocols; Variant; Washington; Waxes; Woman; aged; base; cancer epidemiology; cancer risk; carcinogenesis; case control; cohort; gene function; genetic analysis; improved; ovarian cancer prevention; parity; prevent; response; sample collection; steroid hormone

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.