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 greater than 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 will conduct 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 2200 cases from PanC4 consortium case-control studies on the most promising 100 SNPs using TaqMan. An equal number of controls are included. Additional replication is being conducted in PanScan2 with a full scan on 1600 cases and 1600 controls from cohorts plus approximately 2200 cases and 2200 controls from case-control studies. 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 will begin genotyping for PanScan2 during the winter of 2008/2009. The team plans to produce several manuscripts as part of the joint analysis of the initial scan and replication studies. We anticipate that SNPs highly likely to be markers for genetic variants related to pancreatic cancer risk will emerge from this study 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. In addition, the results from PanScan1 and PanScan2 provide a foundation for subsequent research by the scientific community, including possible applications to understanding familial pancreatic cancer. The results from PanScan1 and PanScan2 are also likely to lead to fine mapping, resequencing, and functional characterization of plausible causal variants. PanScan will offer a unique and powerful potential for meaningful advancement in understanding the cancer""""""""s etiology and prevention. * The PanScan1 cohorts are the: New York University""""""""s Women's Health Study (NYUWHS) """""""" Cancer Prevention Study II (CPS-II), European Prospective Investigation into Cancer and Nutrition Study (EPIC), Shanghai Men""""""""s and Women""""""""s Health Study (SMWHS), Women""""""""s Health Initiative (WHI) , Nurses' Health Study (NHS) , Health Professional's Follow-up Study (HPFS) , Physician's 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 , Women""""""""s 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. 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 greater than 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 will conduct 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 2200 cases from PanC4 consortium case-control studies on the most promising 100 SNPs using TaqMan. An equal number of controls are included. Additional replication is being conducted in PanScan2 with a full scan on 1600 cases and 1600 controls from cohorts plus approximately 2200 cases and 2200 controls from case-control studies. 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 will begin genotyping for PanScan2 during the winter of 2008/2009. The team plans to produce several manuscripts as part of the joint analysis of the initial scan and replication studies. We anticipate that SNPs highly likely to be markers for genetic variants related to pancreatic cancer risk will emerge from this study 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. In addition, the results from PanScan1 and PanScan2 provide a foundation for subsequent research by the scientific community, including possible applications to understanding familial pancreatic cancer. The results from PanScan1 and PanScan2 are also likely to lead to fine mapping, resequencing, and functional characterization of plausible causal variants. PanScan will offer a unique and powerful potential for meaningful advancement in understanding the cancer""""""""s etiology and prevention. * The PanScan1 cohorts are the: New York University""""""""s Women's Health Study (NYUWHS) """""""" Cancer Prevention Study II (CPS-II), European Prospective Investigation into Cancer and Nutrition Study (EPIC), Shanghai Men""""""""s and Women""""""""s Health Study (SMWHS), Women""""""""s Health Initiative (WHI) , Nurses' Health Study (NHS) , Health Professional's Follow-up Study (HPFS) , Physician's 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 , Women""""""""s 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 Hopki [summary truncated at 7800 characters]
| Wolpin, Brian M; Rizzato, Cosmeri; Kraft, Peter et al. (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 46:994-1000 |
