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- Study Description
Within the framework of the NCI-sponsored Cohort Consortium, investigators from 12 prospective epidemiologic cohorts formed the Pancreatic Cancer Cohort Consortium in 2006. This study, also known as "PanScan", is funded by the National Cancer Institute (NCI) and involves conducting a genome-wide association study of common genetic variants to identify markers of susceptibility to pancreatic cancer. In 2007, the study expanded to include 8 case-controls studies. The study team includes scientists from the cohorts comprising the Consortium and NCI and from the PanC4 case-control studies.
The PanScan consortium has conducted two GWAS that have led to the discovery of four novel regions in the genome associated with risk for pancreatic adenocarcinoma. The first two scans were conducted in 12 cohort studies and 8 case-control studies.
Initially, we genotyped 523,345 single nucleotide polymorphisms in 1,528 incident cases and 1,594 controls from nested case-control studies of 12 cohorts plus 368 cases and 345 controls from one hospital-based case-control study. Taqman replication of SNPs from the three most promising regions in the initial scan, as determined by rank p-values, was done in 2,457 cases and 2,654 controls from eight case-control studies that were part of the PanC4 consortium. A combined analysis identified an association between a locus on 9q34 and pancreatic cancer, the single nucleotide polymorphism rs505922 (P= 5.37 x 10-8; multiplicative per-allele odds ratio (OR) 1.20; 95% CI 1.12-1.28), which maps to the first intron of the ABO blood group gene whose protein determines an individual's blood group (Amundadottir et al, Nature Genetics 2009, PMID: 19648918).
In PanScan 2, we conducted a combined analysis of 3,851 pancreatic cancer cases and 3,934 controls. These included 1896 cases and 1939 controls that were scanned in PanScan1 (above) and 1955 cases and 1995 controls that were newly scanned in PanScan2. The second GWAS did not include 502 cases and 659 controls that were part of the rapid replication. (Please see the attached table for the total number of subjects who were GWASed and included in PanScan1 and PanScan2). Three new regions were identified: chromosome 13q22.1 (rs9543325; P=3.27 x 10-11; per-allele odds ratio (OR) 1.26; 95% CI 1.18-1.35); chromosome 1q32.1 in the NR5A2 gene (rs3790844; P=2.45 x 10-10; per-allele OR 0.77; 95% CI 0.71-0.84); and chromosome 5p15.33 (rs401681 in the CLPTM1L and TERT region; P=3.66 x 10-7; per-allele OR 1.19; 95% CI 1.11-1.27). The first two regions have not been identified in GWAS of cancer to date but the last region has been reported to be associated with risk of other malignancies (Petersen et al, Nature Genetics 2010, PMID: 20101243).
- Authorized Access
- Publicly Available Data (Public ftp)
Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.
- Study Inclusion/Exclusion Criteria
Cases will include all incident primary pancreatic adenocarcinomas (ICD-O-3 code C250-C259). Our case definition will exclude endocrine pancreatic tumors (C25.4, histology type, 8150, 8151, 8153, 8155, 8240) because the etiology of these cancers is thought to be different.
- Molecular Data
Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Whole Genome Genotyping Illumina HumanHap550v3.0 561466 51468 Whole Genome Genotyping Illumina Human610_Quadv1_B 601273 1048904
- Study History
The Pancreatic Cancer Cohort Consortium
Each of the 12 member studies of the Cohort Consortium participating in this GWAS is a prospective study of a defined population with blood or buccal cells collected prior to the occurrence of pancreatic cancer. Study characteristics vary but the common and standard prospective cohort design allows for rigorous pooled analysis. Additional information can be found at http://epi.grants.cancer.gov/Consortia/cohort.html. The studies included in PanScan from the Pancreatic Cancer Cohort Consortium are:
ACS Cancer Prevention Study-II (CPS II)
Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC)
European Prospective Investigation into Cancer and Nutrition Study (EPIC)
Give Us a Clue to Cancer and Heart Disease Study (Clue II)
Health Professional's Follow-up Study (HPFS)
NYU Women's Health Study (NYUWHS)
Nurses' Health Study (NHS)
Physicians' Health Study (PHS)
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
Shanghai Men's and Women's Health Study (SMWHS)
Women's Health Initiative (WHI)
The Pancreatic Cancer Case-Control Consortium (PanC4)
Each of the 8 member studies of the PANC4participating in this GWAS is a case-control study of a defined population with blood or buccal cells collected from individuals with pancreatic cancer. It consists of a group of scientists from diverse biomedical disciplines (Epidemiology, Genetics, Biostatistics, Bioinformatics, Molecular Biology, Gastroenterology, Surgery) across the world who have joined together to improve our understanding of the causes of pancreatic cancer through joint, or pooled analyses of our data. Additional information can be found at www.panc4.org. The studies included in PanScan from PanC4 are:
Group Health - Seattle
Johns Hopkins University
Mayo Clinic SPORE in Pancreatic Cancer
MD Anderson Cancer Center
Memorial Sloan Kettering Cancer Center
University of California San Francisco
University of Toronto
- Selected publications
- Diseases/Traits Related to Study (MESH terms)
- Primary Phenotype: Pancreatic Neoplasms
- Authorized Data Access Requests
- Study Attribution