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：
8450223
负责人：
Alison P Klein
金额：
$ 54.78万
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/8450223
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.

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 = 5.9.10-10-10-10-10-10-10-10-1104444444） 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。