The Molecular Epidemiology Of Ovarian Cancer

卵巢癌的分子流行病学

• 批准号: 7751716
• 负责人: Joellen M. SCHILDKRAUT
• 金额: $ 87.21万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751716
• 关键词: Affect; Age; Apoptosis; Biological; Body mass index; Cancer Etiology; Candidate Disease Gene; Case-Control Studies; Clinic; Collaborations; Complement component C1s; Complex; Contraceptive Usage; County; DNA; DNA Repair; DNA Repair Gene; DNA Repair Pathway; Data; Data Analyses; Development; Disease; Early Diagnosis; Epithelial ovarian cancer; Etiology; European; Evaluation Studies; Funding; Future; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genotype; Goals; Heterogeneity; Histology; Hormones; Individual; Intervention; Knowledge; Lead; Los Angeles; Malignant Neoplasms; Malignant neoplasm of ovary; Minor; Modification; Molecular; Molecular Epidemiology; New England; North Carolina; Oral Contraceptives; Ovary; Pathogenesis; Pathway interactions; Phase; Physiological; Predisposition; Pregnancy Histories; Prevention; Race; Research; Risk; Risk Factors; Role; Sampling; Serous; Single Nucleotide Polymorphism; Staging; Subgroup; Variant; Woman; Work; base; cancer risk; design; disorder risk; genetic variant; improved; insight; mortality; population based; prevent; repaired; response

In the current funding period of our study entitled ‘The Molecular Epidemiology of Ovarian Cancer’ (RO1CA176016, PI: Dr. Schildkraut,), we have studied the relationship between candidate genes in the DNA damage and repair pathway and ovarian cancer risk using data from the North Carolina Ovarian Cancer Study (NCOCS). To date, we have examined the relationship between 53 genes and 652 SNPs in this pathway. The first phase of our study we have identified strong association between genes on the DNA repair pathway and ovarian cancer risk. In this competitive renewal we propose to expand the scope of our Phase 1 genotyping to further investigate genes the DNA repair and apopotosis pathways and to mount a second candidate gene association study. We hypothesize that a subset of the previouslyexamined SNPs in genes with known roles in DNA damage and repair will emerge as risk factors for ovarian cancer, and that newly-examined SNPs in genes within this and related pathways will be associated with risk of ovarian cancer. The proposed study will be designed to optimally accumulate evidence on candidates while simultaneously reducing the false positive rate among included SNPs and minimizing the rate of false negatives. Analyses will examine risk modification across subgroups defined by age, race, body mass index, oral contraceptive use, pregnancy history, histology and other exposures. The ultimate goal is to improve our ability to identify women at genetic risk of ovarian cancer and to design targeted intervention strategies to prevent this fatal disease. To this end, we propose to genotype in 2,075 invasive serous epithelial ovarian cancer cases and 2,075 age-matched controls of European descent to determine the relationship between genetic variants in DNA response and repair and related pathways. We will evaluate the association between over 2,000 SNPs with risk of ovarian cancer. We will access subjects from six independent case-control studies: North Carolina (Dr.Schildkraut), the Mayo Clinic (Dr. Goode), New England (Drs. Terry and Cramer), Pittsburgh (Dr. Ness), Los Angeles (Drs. Pearce and Wu) and Seattle (Dr. Rossing). Further confirmation will be pursued in collaboration with the Ovarian Cancer Association Consortium (OCAC) in the future.

在我们题为《卵巢癌的分子流行病学》的研究的当前资助期内 (RO1CA176016，PI：Dr.Sylkraut，)，我们研究了候选基因之间的关系。 来自北卡罗来纳州卵巢的数据显示DNA损伤和修复途径与卵巢癌风险 癌症研究(NCOCS)。到目前为止，我们已经研究了53个基因和652个SNPs之间的关系 这条路。在我们研究的第一阶段，我们已经确定了基因之间的强烈关联 DNA修复途径与卵巢癌风险。在这次竞争性续签中，我们建议扩大范围 我们的第一阶段基因分型，以进一步研究基因，DNA修复和细胞凋亡途径，并 开展第二项候选基因关联研究。我们假设之前检查的一部分 在DNA损伤和修复中具有已知作用的基因中的SNPs将成为 卵巢癌，以及新检查的这一途径和相关途径中的基因SNPs将是 与卵巢癌的风险有关。拟议的研究将设计为以最佳方式积累 同时降低包含的SNPs中的假阳性率 并将假阴性率降至最低。分析将检查子组之间的风险修改 由年龄、种族、体重指数、口服避孕药使用、孕产史、组织学和其他因素定义 曝光。最终目标是提高我们识别卵巢癌遗传风险女性的能力。 并设计有针对性的干预策略来预防这种致命的疾病。为此，我们建议 2,075例浸润性浆液性上皮性卵巢癌患者和2,075例年龄匹配的对照 欧洲血统，以确定DNA反应和修复中的遗传变异与 相关的路径。我们将评估2000多个SNP与卵巢癌风险的关系。 我们将从六个独立的病例对照研究中获取受试者：北卡罗来纳州(斯奇尔克劳特博士)， 梅奥诊所(古德博士)，新英格兰(特里和克雷默博士)，匹兹堡(内斯博士)，洛杉矶(博士。 皮尔斯和吴)和西雅图(罗辛博士)。将与以下机构合作进行进一步确认 卵巢癌协会联合会(OCAC)在未来。