Within the framework of the NCI-sponsored Cohort Consortium, investigators from 12 prospective epidemiologic cohorts* have formed the Pancreatic Cancer Cohort Consortium. This study, also known as PanScan, is funded by the National Cancer Institute (NCI) and involves conducting a genome-wide association study (GWAS) of common genetic variants to identify markers of susceptibility to pancreatic cancer. The study team includes scientists from the cohorts comprising the Consortium and NCI. The team plans to analyze a dense set of the most common genetic variants in the human genome, single nucleotide polymorphisms (SNPs) with sufficiently high enough minor allele frequencies (MAF >5%). The panel of SNPs is based on an analysis of common SNPs in individuals of northern European background determined by the International HapMap Project and provides an opportunity to monitor tested and untested SNPs because of linkage disequilibrium in the genome. It is estimated that the current panel of markers for a whole genome scan includes 550,000 SNPs and serves as markers for approximately 90% of all common SNPs in Europeans. PanScan1 was a GWAS of 550,000 SNPs in a case-control study nested in the prospective cohorts on 1600 incident pancreatic cancer cohort consortium cases plus 400 clinic-based cases from the Mayo Clinic Molecular Epidemiology of Pancreatic Cancer Case-Control Study followed by a rapid relication of the the most promising 100 SNPs using TaqMan on 2200 cases from PanC4 consortium* of case-control studies. An equal number of controls are included. A combined analysis is in progress in PanScan2 with a the full scan on 1600 cases and 1600 controls from cohorts plus approximately 2400 cases and 2400 controls from case-control studies in PanC4. It is anticipated that additional replication studies in other cohorts and case-control groups will follow these scans. The NCI Core Genotyping Facility has conducted genotyping for PanScan1 and for PanScan2. The team plans has produced or plans to produce several manuscripts as part of the joint analysis of the initial scan and second scan. In PanScan1, we identified variants in the ABO locus to be associated with pancreatic cancer and anticipate that additional SNPs highly likely to be markers for genetic variants related to pancreatic cancer risk will emerge from PanScan2 and lead to further studies of gene-gene, gene-environment, and gene-lifestyle interactions with pancreatic cancer risk factors, including known exposures and biomarkers collected on these individuals. The results from PanScan1 and PanScan2 has led to fine mapping, resequencing, and functional characterization of our initial variants identified. PanScan will offer a unique and powerful potential for meaningful advancement in understanding the cancers etiology and prevention. * These cohorts are the: New York Universitys Women's Health Study (NYUWHS) , Cancer Prevention Study II (CPS-II), European Prospective Investigation into Cancer and Nutrition Study (EPIC), Shanghai Mens and Womens Health Study (SMWHS), Womens Health Initiative (WHI) Nurses'Health Study (NHS) Health Professional's Follow-up Study (HPFS) Physicians Health Study (PHS), Give Us a Clue to Cancer and Heart Disease Study (Clue II), Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC), Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial , Womens Health Study (WHS). PanC4 is a group of investigators from many case-control studies. Eight of these studies are participating in PanScan I and PanScan2: The University of Toronto, University of California San Francisco, Johns Hopkins University, MD Anderson Cancer Center, Group Health Seattle, Memorial Sloan Kettering Cancer Center, Yale University, and the Mayo Clinic.
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