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Genome-wide Case-control Association Study of Pancreatic Cancer in Jews

犹太人胰腺癌的全基因组病例对照关联研究

基本信息

批准号：
8788231
负责人：
Samantha Acson Streicher
金额：
$ 4.31万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-11-16 至 2016-01-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8788231
关键词：
1q32.1 5p15.33 7q36 9q34 Accounting African American Ashkenazim BRCA1 Mutation BRCA1 gene BRCA2 Mutation Blood typing procedure Cancer Etiology Candidate Disease Gene Connecticut Data Data Set Diabetes Mellitus Disease Early Diagnosis Epidemiologic Studies Ethnic Origin Ethnic group Family Gene Mutation Genes Genetic Genetic Markers Genetic Screening Genetic Techniques Genetic Variation Growth Individual Israel Jews Logistic Regressions Malignant neoplasm of pancreas Maps Methods Modeling Mutation Obesity Outcome Pancreas Participant Pathway interactions Patient Self-Report Pattern Population Predisposition Prevalence Principal Component Analysis Race Recording of previous events Religion and Spirituality Research Risk Risk Factors Sample Size Single Nucleotide Polymorphism Smoking Survival Rate Time United States Universities Validation Variant Woman Work base blood group carcinogenesis case control chronic pancreatitis cohort follower of religion Jewish gene environment interaction gene interaction genetic variant genome wide association study genome-wide high risk human SHH protein men mortality pancreatic neoplasm programs public health relevance racial and ethnic screening

项目摘要

DESCRIPTION (provided by applicant): Epidemiologic studies have consistently found Jews to be at increased risk of pancreatic cancer compared to non-Jewish whites. This excess risk is not accounted for by BRCA1/2 mutations or by other known risk factors. We therefore propose to examine in Jewish subjects the most significant single nucleotide polymorphism (SNP) associations observed in the Pancreatic Cancer Cohort and Case-Control Consortium (PanScan) genome-wide association study (GWAS), to perform an exploratory GWAS to identify additional SNPs associated with pancreatic cancer in the Jewish population, and to assess genetic underpinning of the relationship between Jewish ancestry and pancreatic cancer. To do this, we will use GWAS data from PanScan and from the Johns Hopkins University study titled "Validation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci." In our study, Jewish subjects with be identified with a panel of genetic markers that correlate strongly with self-reported Jewish ancestry. Preliminary sample size calculations, based upon participants in the PanScan and Johns Hopkins University studies, give an estimate of around 500 Jewish cases and 300 unaffected Jewish controls. We will use the program Eigensoft (v.3.0) to conduct a principal component analysis that will genetically identify Jewish subjects among other racial/ethnic groups. We will validate these genetically identified Jews by using a subset of self-reported Jewish subjects in the Yale University, Johns Hopkins, and Memorial Sloan Kettering studies, all sub-studies in the PanScan and Johns Hopkins University studies. We will perform the SNP replication analysis, conduct the GWAS, and will assess genetic contribution using the program PLINK (v.1, 07): whole genome association analysis toolset. Logistic regression models will be used for each SNP, with pancreatic cancer as the outcome variable and each SNP as a predictor variable. Any association with P-value less than 0.05 will be considered significant for the candidate gene approach, and less than 10-6 for the GWAS approach. This will be the first study to determine a genetic basis, distinct from BRCA1/2 mutations, for the excess risk of pancreatic cancer in Jews. Results from this work will open paths to identify genetic interactions and will begin to approach the possibility of genetic screening for pancreatic cancer in the Jewish population.

描述（由申请人提供）：流行病学研究一直发现，与非犹太白人相比，犹太人患胰腺癌的风险增加。这种额外的风险不是由BRCA 1/2突变或其他已知的风险因素引起的。因此，我们建议在犹太受试者中检查胰腺癌队列和病例对照联盟（PanScan）全基因组关联研究（GWAS）中观察到的最显著的单核苷酸多态性（SNP）关联，进行探索性GWAS以确定犹太人群中与胰腺癌相关的其他SNP，并评估犹太血统与胰腺癌之间关系的遗传基础。为此，我们将使用来自PanScan和约翰霍普金斯大学题为“胰腺癌易感基因的验证和精细定位”的研究的GWAS数据。“在我们的研究中，犹太受试者被鉴定出一组与自我报告的犹太血统密切相关的遗传标记。根据PanScan和约翰霍普金斯大学研究的参与者进行的初步样本量计算，估计约有500例犹太病例和300例未受影响的犹太对照。我们将使用程序Eigensoft（v.3.0）进行主成分分析，该分析将在其他种族/族裔群体中从遗传学上识别犹太受试者。我们将使用耶鲁大学、约翰霍普金斯大学和纪念斯隆凯特琳研究中自我报告的犹太受试者子集来验证这些基因识别的犹太人，这些研究都是PanScan和约翰霍普金斯大学研究中的子研究。我们将进行SNP复制分析，进行GWAS，并将使用程序PLINK（v.1，07）：全基因组关联分析工具集评估遗传贡献。逻辑回归模型将用于每个SNP，胰腺癌作为结果变量，每个SNP作为预测变量。对于候选基因方法，P值小于0.05的任何关联将被认为是显著的，对于GWAS方法，P值小于10-6的任何关联将被认为是显著的。这将是第一项确定犹太人胰腺癌过度风险的遗传基础的研究，与BRCA 1/2突变不同。这项工作的结果将开辟途径，以确定遗传相互作用，并将开始接近的可能性，遗传筛查胰腺癌的犹太人口。