PanScan, the Pancreatic Cancer Cohort Consortium, and the Pancreatic Cancer Case-Control Consortium

The Pancreatic Cancer Cohort Consortium consists of more than a dozen prospective epidemiologic cohort studies within the NCI Cohort Consortium, whose leaders work together to investigate the etiology and natural history of pancreatic cancer. They formed the Pancreatic Cancer Cohort Consortium in 2006 by investigators for the initial purpose of launching a genome-wide association study (PanScan). The PanScan study has expanded to include a collaboration with investigators leading eight hospital-based case-control studies that belong to the Pancreatic Cancer Case-Control (PANC4) Consortium.

No effective screening test exists for pancreatic cancer, which is one of the leading causes of cancer mortality in the United States. It is often diagnosed at an advanced stage, contributing to a 5-year survival rate of less than 5 percent. NCI’s research priorities include the identification of genetic factors, environmental exposures, and gene-environment interactions that contribute to the development of this cancer, and identification and development of methods of surveillance and diagnosis for early detection of the disease. Both consortia seek to address these priorities.

PanScan investigators have conducted two genome-wide association studies (GWAS), PanScan I and PanScan II, that have led to the discovery of four novel regions in the genome associated with risk for pancreatic cancer (Amundadottir et al., Nature Genetics 2009External Web Site Policy; Petersen et al., Nature Genetics 2010External Web Site Policy). PanScan I and II were conducted with pancreatic cancer cases and controls from 12 prospective epidemiology cohort studies and one case-control study.

The third phase of the project, PanScan III, will analyze more than 3,000 pancreatic cancer cases from 14 cohorts, including those from PanScan I and II, and four new cohorts, to discover novel regions of the genome associated with pancreatic cancer susceptibility. PanScan III will include approximately 1,620 new incident pancreatic cancer cases from prospective cohorts and, 780 cases from three clinic-based case-control studies, for a total of approximately 2,400 additional cases for genome-wide scanning.

PanScan III investigators are also requesting permission to use genotyping data from controls without previous pancreatic cancer that were part of previous GWAS studies from all cohorts participating in PanScan I or PanScan III (17 cohorts in total). Genotyping will be performed at the Cancer Genomics Research (CGR) Laboratory of the Division of Cancer Epidemiology and Genetics (DCEG) at the NCI using the Illumina Human OmniExpress 770-Quad genotyping platform. The SNP content on the Illumina Human OmniExpress 770-Quad chip is based on an analysis of common SNPs in individuals of mostly 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.

In a replication study, PanScan III will also genotype the top 20-50 loci from the GWAS in 329 cases from four cohorts: CARET (n=50 cases, 50 controls), Melbourne (n=70 cases), ATBC Study (n=91 cases), and VITAL (n=89 cases) cohorts; 2,100 cases and 3,500 controls from the European PANDoRA case-control consortium consisting of 18 different hospital-based sites within Europe; and 350 cases CALGB 80303, a GWAS of advanced pancreatic cancer patients.

A joint analysis of the newly scanned cases will be conducted with cases from PanScan I and II to identify novel regions of the genome associated with pancreatic cancer susceptibility. With the larger sample size (about 6,200 cases and 13,900 controls), the PanScan III investigators anticipate that they will identify new genetic risk variants for etiology. It is notable that this study will include about 3,200 incident cases from the Cohort Consortium, which are more likely to represent the diversity of pancreatic cancers at presentation.

The investigators have made genotype results and individual SNP analyses available to other researchers. Researchers may apply for access through the CGEMS Pancreatic Cancer Data Web pageExternal Web Site Policy; please direct questions to ncicgems@mail.nih.gov. The efforts of the grant-supported cohorts are coordinated by Dr. Charles Fuchs, those of the grant-supported case-control studies by Dr. Gloria Peterson, and those of NCI-led intramural studies by Dr. Rachael Stolzenberg-Solomon.

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