Searching for new risk variants in known breast cancer risk loci in Asians

在亚洲人已知的乳腺癌风险位点中寻找新的风险变异

基本信息

批准号：
8638596
负责人：
Jirong Long
金额：
$ 7.85万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-19 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638596
关键词：
Architecture Asia Asians Breast Cancer Genetics Breast Cancer Prevention Cancer Biology Complex DNA Data Data Analyses Diagnosis Disease Environment Ethnic group Etiology European Gene Frequency Genes Genetic Genetic Predisposition to Disease Genetic Risk Genome Genotype Hereditary Breast Carcinoma High Risk Woman International Investigation Linkage Disequilibrium Malignant Neoplasms Meta-Analysis Methodology Other Genetics Parents Play Population Prevention strategy Recruitment Activity Reporting Research Design Resources Risk Assessment Role Sample Size Sampling Screening for cancer Signal Transduction Staging Structure Variant Woman base cancer genetics cancer risk cancer therapy case control cost design genetic risk factor genetic variant genome wide association study improved indexing malignant breast neoplasm new technology next generation sequencing novel public health relevance risk variant tool

项目摘要

DESCRIPTION (provided by applicant): Genetic factors play an important role in the etiology of breast cancer, a complex, multifactorial disease. To date, genome-wide association studies (GWAS) have discovered approximately 67 common genetic susceptibility loci for breast cancer risk. However, with the exception of a few loci, all others were identified initially in studies conducted among women of European ancestry. Among the 67 index SNPs reported to date, only about a half of them could be directly replicated in Asians. Given differences in genetic architecture across different ethnic populations, we hypothesize that different risk variants may exist in Asian-ancestry populations in some of the loci in which the index SNPs were not replicated in Asians. Multiple studies have showed that imputation based on the 1000 Genomes Project data provides better chance to identify novel risk variants than that based on the HapMap data since data in the 1000 Genomes Project have much denser SNPs especially low allele frequency SNPs and a larger sample size. Over the past few years, we have genotyped ~9,400 breast cancer cases and controls of Asian ancestry using Affymetrix 6.0 SNP arrays. We propose to impute data for these samples using the most recent 1,000 Genomes Project data as reference to evaluate 10 breast cancer loci in which the index SNPs were not replicated in Asians. Promising SNPs will be further investigated in an independent set of 8,400 cases and controls of Asian ancestry. With strong methodology and very cost- efficient study design, we anticipate that novel genetic variants will be identified in these loci in Asian ancestry populations. These newly-identified variants could significantly improve our understanding of breast cancer genetics and biology and could be used for cancer screening and risk assessment aimed at identifying high- risk women for targeted breast cancer prevention.

描述（由申请人提供）：遗传因素在乳腺癌（一种复杂的多因素疾病）的病因中起重要作用。迄今为止，全基因组关联研究（GWAS）发现了大约67个常见的遗传易感性基因座用于乳腺癌风险。但是，除了一些基因座外，所有其他基因座最初都在欧洲血统的妇女中进行的研究中被确定。在迄今为止据报道的67个指数SNP中，只有大约一半的亚洲人可以直接复制。鉴于在不同种族人群之间的遗传结构差异，我们假设在亚洲人的某些基因座中，亚洲人的种群中可能存在不同的风险变异，在亚洲人中未重复索引SNP。多项研究表明，基于1000个基因组项目数据的插补提供了比基于HAPMAP数据的机会更好的机会来识别新型风险变异，因为1000个基因组项目中的数据具有较密集的SNP，尤其是低等位基因频率SNP和更大的样本量。在过去的几年中，我们使用Affymetrix 6.0 SNP阵列进行了约9,400例乳腺癌病例和亚洲血统的控制。我们建议使用最新的1,000个基因组项目数据为这些样品汇总数据，以评估10个乳腺癌基因座，其中未在亚洲人中复制索引SNP。有希望的SNP将在一个独立的8,400例亚洲血统的案例和控制中进一步研究。通过强大的方法论和非常具有成本效益的研究设计，我们预计在亚洲血统人群中将在这些基因座中确定新的遗传变异。这些新识别的变体可以显着提高我们对乳腺癌遗传学和生物学的理解，并可用于癌症筛查和风险评估，旨在鉴定有针对性的乳腺癌预防妇女。