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）：胰腺癌是美国第四大癌症死亡原因。这在很大程度上是由于该病的病程迅速致命，绝大多数患者在诊断后数月内死亡，五年生存率低于 5%。与所有癌症一样，胰腺癌从根本上来说是一种由遗传性和获得性基因突变引起的遗传性疾病。最近完成了两项胰腺癌全基因组关联研究 PanScan I 和 PanScan II。这些研究确定了与胰腺癌易感性相关的四个有前景的区域：ABO rs505922 (P=4.3.10-6)、染色体 13q22.1 上的两个相关 SNP、rs9543325 (P=3.3.10-11) 和 rs9564966 (P=5.9) .10-8), rs3790844 (P=2.4.10-10) 位于染色体 1q32.1 上，rs401681 (P=3.7.10-7) 位于 5p15.33 上。该项目的目标是对最近完成的 PanScan I 和 PanScan II 研究中确定的潜在胰腺癌易感性变异进行精细绘图和大规模验证基因分型，这些变异来自 10 多项研究的 4,000 例独立病例和 4,000 例对照。这将是这些发现的首次大规模复制。还将对这些数据与 PanScanI 和 II 的数据进行联合分析。我们还将确定胰腺癌的已知危险因素，包括吸烟和糖尿病，这些因素会改变这些关联。公共卫生相关性：全基因组关联研究 (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、前列腺癌和结肠癌中发挥重要作用的基因，但其中第一项针对胰腺癌的研究最近才完成。在将这些研究的结果转化为患者环境之前，需要对最初的研究结果进行复制，以确定 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 研究也有可能发现新的关联。因此，本研究的目标是验证最初的胰腺癌 GWAS 研究结果，并确定可能与胰腺癌相关的新 DNA 变化。