Validation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci

胰腺癌易感性位点的验证和精细绘图

基本信息

批准号：
8249831
负责人：
Alison P Klein
金额：
$ 59.94万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8249831
关键词：
1q32.1 5p15.33 BRCA2 gene Cancer Etiology Cancer Patient Case-Control Studies Cessation of life Chromosomes Collection Colon Carcinoma Custom DNA Data Data Analyses Development Diabetes Mellitus Diagnosis Disease Epidemiology Europe Family history of Gene Frequency Gene Mutation Genes Genetic Genome Genotype Goals Hereditary Disease Individual Inherited Joints Malignant Neoplasms Malignant neoplasm of pancreas Malignant neoplasm of prostate Maps Pancreatitis Pathway interactions Patients Penetrance Play Predisposition Recording of previous events Risk Risk Factors Role Signal Transduction Single Nucleotide Polymorphism Map Smoking Survival Rate Susceptibility Gene Translating United States Validation Variant base cancer genome cancer risk case control cigarette smoking follow-up genetic analysis genome wide association study genome-wide high risk improved malignant breast neoplasm member novel public health relevance tool

项目摘要

DESCRIPTION (provided by applicant): Pancreatic cancer is the 4th leading cause of cancer death in the United States. This is in large part due to the rapidly fatal course of this disease, as the vast majority of patients die within months of diagnosis and the five- year survival rate is less than 5%. Like all cancers, pancreatic cancer is a fundamentally genetic disease caused by inherited and acquired genetic mutations. Two genome-wide association studies of pancreatic cancer, PanScan I and PanScan II, have recently been completed. These studies have identified four promising regions involved in pancreatic cancer susceptibility: ABO rs505922 (P=4.3.10-6), two correlated SNPs on chromosome 13q22.1, rs9543325 (P=3.3.10-11) and rs9564966 (P=5.9.10-8), rs3790844 (P=2.4.10-10) on chromosome 1q32.1, and rs401681 (P=3.7.10-7) on 5p15.33. The goal of this project is to conduct fine-mapping and large-scale validation genotyping of the potential pancreatic cancer susceptibility variants identified in the recently completed PanScan I and PanScan II studies, in an independent set of 4,000 cases and 4,000 controls from over 10 studies. This will be the first well-powered large-scale replication of these findings. Joint-analysis of these data with the data from PanScanI and II will also be conducted. We will also determine known risk factors for pancreatic cancer including, cigarette smoking and diabetes modify these associations. PUBLIC HEALTH RELEVANCE: Genome-wide association studies (GWAS) are powerful tools to identify changes in DNA associated with diseases. These studies have identified many genes that play an important role in breast, prostate and colon cancers but the first of these studies have only recently been completed for pancreatic cancer. Before the findings of these studies can be translated into the patient setting, replication of the initial findings needs to be conducted to establish that changes in DNA are "truly" associated with pancreatic cancer, not false findings. Furthermore, follow-up GWA studies also have the potential to identify novel associations. Therefore the goal of this study will be to validate the initial pancreatic cancer GWAS findings and identify novel DNA changes that may be associated with pancreatic cancer.

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四个主要原因。这在很大程度上是由于这种疾病的迅速致命病程，因为绝大多数患者在诊断后的几个月内死亡，五年生存率小于5％。像所有癌症一样，胰腺癌是由遗传和获得的遗传突变引起的根本遗传疾病。最近完成了两项胰腺癌全基因组关联研究，即Panscan I和Panscan II。这些研究已经确定了胰腺癌易感性涉及的四个有前途的区域：ABO RS505922（p = 4.3.10-6），两个在13q22.1染色体上的SNP相关的SNP，RS9543325（rs9543325）（p = 3.3.10-11）和RS9564966（p = 5.9.10-10-10-10-10-10-10-10-1104444444444444444444444444444444444444444444444444444 oon of 5p15.33上的1q32.1染色体1q32.1和RS401681（p = 3.7.10-7）。该项目的目的是在最近完成的Panscan I和Panscan II研究中确定的潜在胰腺癌易感性变体进行精细映射和大规模验证基因分型，并在10多个研究中的4,000例和4,000例对照中进行。这将是这些发现的第一个大规模复制。这些数据的联合分析也将与潘塞尼和II的数据进行。我们还将确定胰腺癌的已知危险因素，包括吸烟和糖尿病会改变这些关联。公共卫生相关性：全基因组协会研究（GWAS）是识别与疾病相关的DNA变化的强大工具。这些研究已经确定了许多在乳腺癌，前列腺和结肠癌中起重要作用的基因，但是这些研究中的第一个直到最近才完成胰腺癌。在将这些研究的发现转化为患者环境之前，需要对初始发现的复制来确定DNA的变化与胰腺癌“真正”相关，而不是错误的发现。此外，后续GWA研究还具有识别新型关联的潜力。因此，这项研究的目的是验证最初的胰腺癌GWAS发现，并确定可能与胰腺癌相关的新型DNA变化。