|Grant Number:||5R01CA154823-03 Interpret this number|
|Primary Investigator:||Klein, Alison|
|Organization:||Johns Hopkins University|
|Project Title:||Validation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci|
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.
Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer.
Authors: Roberts N.J. , Norris A.L. , Petersen G.M. , Bondy M.L. , Brand R. , Gallinger S. , Kurtz R.C. , Olson S.H. , Rustgi A.K. , Schwartz A.G. , et al. .
Source: Cancer discovery, 2016 Feb; 6(2), p. 166-75.
EPub date: 2015-12-09.
Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
Authors: Childs E.J. , Mocci E. , Campa D. , Bracci P.M. , Gallinger S. , Goggins M. , Li D. , Neale R.E. , Olson S.H. , Scelo G. , et al. .
Source: Nature genetics, 2015 Aug; 47(8), p. 911-6.
EPub date: 2015-06-22.
TERT gene harbors multiple variants associated with pancreatic cancer susceptibility.
Authors: Campa D. , Rizzato C. , Stolzenberg-Solomon R. , Pacetti P. , Vodicka P. , Cleary S.P. , Capurso G. , Bueno-de-Mesquita H.B. , Werner J. , Gazouli M. , et al. .
Source: International journal of cancer, 2015-11-01; 137(9), p. 2175-83.
EPub date: 2015-06-19.
Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.
Authors: Tang H. , Wei P. , Duell E.J. , Risch H.A. , Olson S.H. , Bueno-de-Mesquita H.B. , Gallinger S. , Holly E.A. , Petersen G.M. , Bracci P.M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Jan; 23(1), p. 98-106.
EPub date: 2013-10-17.
An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
Authors: Klein A.P. , Lindström S. , Mendelsohn J.B. , Steplowski E. , Arslan A.A. , Bueno-de-Mesquita H.B. , Fuchs C.S. , Gallinger S. , Gross M. , Helzlsouer K. , et al. .
Source: PloS one, 2013; 8(9), p. e72311.
EPub date: 2013-09-13.
Recent progress in pancreatic cancer.
Authors: Wolfgang C.L. , Herman J.M. , Laheru D.A. , Klein A.P. , Erdek M.A. , Fishman E.K. , Hruban R.H. .
Source: CA: a cancer journal for clinicians, 2013 Sep; 63(5), p. 318-48.
EPub date: 2013-07-15.
Identifying people at a high risk of developing pancreatic cancer.
Authors: Klein A.P. .
Source: Nature reviews. Cancer, 2013 Jan; 13(1), p. 66-74.
EPub date: 2012-12-06.
Genome-wide sequencing to identify the cause of hereditary cancer syndromes: with examples from familial pancreatic cancer.
Authors: Roberts N.J. , Klein A.P. .
Source: Cancer letters, 2013-11-01; 340(2), p. 227-33.
EPub date: 2012-11-27.
Identification of germline genomic copy number variation in familial pancreatic cancer.
Authors: Al-Sukhni W. , Joe S. , Lionel A.C. , Zwingerman N. , Zogopoulos G. , Marshall C.R. , Borgida A. , Holter S. , Gropper A. , Moore S. , et al. .
Source: Human genetics, 2012 Sep; 131(9), p. 1481-94.
EPub date: 2012-06-05.