Genome-Wide Association Study of Endometrial Cancer

子宫内膜癌全基因组关联研究

• 批准号: 7725761
• 负责人: Immaculata De Vivo
• 金额: $ 216.79万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725761
• 关键词: Alberta province; American Cancer Society; Anabolism; Body mass index; California; Cancer Prevention Study II; Cancer and Nutrition; Candidate Disease Gene; Case-Control Studies; Complex; Connecticut; Contraceptive Usage; DNA Repair; Data; Diet; Disease; Endometrial; Endometrial Carcinoma; Enrollment; Ensure; Environmental Risk Factor; Epidemiology; Estrogens; Ethnic Origin; Etiology; European; Exogenous Hormone Therapy; Exposure to; Family history of; Fred Hutchinson Cancer Research Center; Future; Gene Frequency; Genes; Genetic; Genotype; Goals; Growth Factor; Heterogeneity; Hormones; Inherited; International; Investigation; Malignant Neoplasms; Metabolism; Modification; Nurses' Health Study; Odds Ratio; Oral Contraceptives; Pathway interactions; Play; Polishes; Positioning Attribute; Postmenopause; Prevention; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Reproductive History; Retrospective Studies; Risk; Risk Factors; Role; Sample Size; Sampling; Scanning; Specimen; Staging; Testing; United States; Woman; cancer risk; case control; cohort; experience; factor A; genetic variant; genome wide association study; genome-wide; insight; markov model; novel; prospective; public health relevance; teacher

DESCRIPTION (provided by applicant): We propose to conduct a genome-wide association study to identify loci involved in endometrial cancer causation. We plan to utilize studies with available biospecimens, 6 cohorts from the NCI Cohort Consortium and 7 case-control studies, within the NCI Epidemiology of Endometrial Cancer Consortium, by far the largest international collaborative study of this cancer, the 4th most common in the U.S. Given the large sample size of the combined studies of whites and nonwhites, the best scientific approach to study the role of genetic variants is to pool existing studies of endometrial cancer. To this end we are proposing to conduct the initial genome- wide scan in 2,307 white cases of European descent and 2,307 matched controls using the Illumina HumanHap 610K platform. After the initial scan, we plan to genotype approximately 7,000 markers showing the strongest evidence for association with risk of endometrial cancer in a multiethnic replication sample of 3,258 cases and 3,258 matched controls. The large overall sample size and the large number of markers to be genotyped in the replication samples ensures that we will have very good power to detect the modest marginal genetic effects expected for complex diseases. We will have over 80 percent power in whites (at the genome-wide significance level of 1W10-7) to detect multiplicative odds ratios between 1.19 and 1.30 for risk allele frequencies between 10 percent and 40 percent. In the third characterization stage, we will genotype approximately 60 SNPs in those regions that achieve genome-wide significance in an additional multiethnic sample of 874 cases and 874 controls. Our sample size will also give us the unique opportunity to evaluate effect modification by known risk factors (e.g. body mass index, postmenopausal hormone use, oral contraceptive use) and assess heterogeneity in risk across ethnicity. PUBLIC HEALTH RELEVANCE: Project Narrative Endometrial cancer, the most common gynecological malignancy in the United States, has both an environmental and genetic component. To this end, we propose to conduct a genome-wide association study to identify genes involved in endometrial cancer. We plan to utilize existing studies; they include 6 cohort and 7 case control with a total sample size of 6,439 cases and 6,439 matched controls through 2007. The overall goal is to determine whether certain genotypes are predictive of future endometrial cancer risk, and whether the genotypes interact with established endometrial risk factors.

描述（由申请人提供）：我们建议进行全基因组关联研究，以确定与子宫内膜癌病因相关的位点。我们计划利用现有生物标本的研究，来自NCI队列联盟的6个队列和NCI子宫内膜癌流行病学联盟的7个病例对照研究，这是迄今为止该癌症最大的国际合作研究，在美国排名第四。考虑到白人和非白人联合研究的大样本量，研究遗传变异作用的最佳科学方法是汇集现有的子宫内膜癌研究。为此，我们建议使用Illumina HumanHap 610K平台对2307例欧洲血统的白人病例和2307例匹配的对照进行初始全基因组扫描。在初始扫描后，我们计划对大约7000个标记物进行基因分型，在3258例多种族复制样本和3258例匹配对照中显示与子宫内膜癌风险相关的最有力证据。大的总体样本量和在复制样本中进行基因分型的大量标记确保我们将有很好的能力来检测复杂疾病预期的适度边际遗传效应。在白人中，我们将有超过80%的能力（在全基因组显著性水平为1W10-7的情况下）检测到风险等位基因频率在10%到40%之间的倍增优势比在1.19到1.30之间。在第三个表征阶段，我们将在额外的874例病例和874例对照的多种族样本中，对这些区域中达到全基因组意义的约60个snp进行基因型分析。我们的样本量也将为我们提供独特的机会来评估已知风险因素（如体重指数、绝经后激素使用、口服避孕药使用）对效果的影响，并评估不同种族风险的异质性。子宫内膜癌是美国最常见的妇科恶性肿瘤，它既有环境因素，也有遗传因素。为此，我们建议开展全基因组关联研究，以确定与子宫内膜癌相关的基因。我们计划利用现有的研究；它们包括6个队列和7个病例对照，总样本量为6,439例，到2007年为6,439例匹配对照。总体目标是确定某些基因型是否可以预测未来子宫内膜癌的风险，以及这些基因型是否与既定的子宫内膜危险因素相互作用。