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. PanScan will conduct a GWAS of 550,000 SNPs in a case-control study nested in the prospective cohorts with 1600 incident pancreatic cancer cases and 1600 controls in total. A simultaneous validation study will use the same 550,000 SNP platform to genotype 400 incident, clinic-based cases and 400 controls from the Mayo Clinic Molecular Epidemiology of Pancreatic Cancer Case-Control Study. It is anticipated that additional replication studies in other cohorts and case-control groups will follow these initial scans. The NCI Core Genotyping Facility will begin conducting genotyping for PanScan in the summer of 2007. To accelerate the pace of discovery and characterization of genetic markers associated with pancreatic cancer risk, the results of the GWAS and validation study will be made available to the research community. The team plans to produce several manuscripts as part of the joint analysis of the initial scan and validation study. In addition, they will post the genotyping results on a controlled-access web site, available to the biomedical research community. It is expected that the results will be posted in the spring of 2008. 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, PanScan may provide a foundation for subsequent research by the scientific community, including possible applications to understanding familial pancreatic cancer. The prompt posting of results is 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 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) 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 Womens Health Study (WHS
| 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 |
