Validation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四大原因。这在很大程度上是由于这种疾病的快速致命过程，因为绝大多数患者在诊断后几个月内死亡，五年生存率低于5%。与所有癌症一样，胰腺癌是一种由遗传和获得性基因突变引起的基本遗传性疾病。最近完成了两项胰腺癌全基因组关联研究PanScan I和PanScan II。这些研究已经确定了四个与胰腺癌易感性有关的有希望的区域：ABO rs505922（P=4.3.10-6），染色体13q22.1上的两个相关SNP，rs 9543325（P=3.3.10-11）和rs 9564966（P=5.9.10-8）、rs3790844（P=2.4.10-10）和rs 401681（P=3.7.10-7）位于染色体1q32.1和5p15.33。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体进行精细定位和大规模验证基因分型，这些研究包括来自10多项研究的4，000例病例和4，000例对照。这将是这些发现的第一次有力的大规模复制。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风险因素，包括吸烟和糖尿病改变这些关联。

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.