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Genome-wide association study of renal cell carcinoma: replication scan

Principal Investigator
Name
Mark Purdue
Degrees
-
Institution
NCI, DCEG, OEEB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2007-0253
Initial CDAS Request Approval
May 9, 2008
Title
Genome-wide association study of renal cell carcinoma: replication scan
Summary
A genome-wide scan of 317,000 SNPs recently completed within a large Eastern European case-control study of renal cell carcinoma (RCC; 1,150 cases and 2,200 controls) is poised to greatly advance our understanding of the contribution of genetic factors to the pathogenesis of this cancer. A critical next step will be to investigate which of the associations observed from this scan are replicable in other studies, in light of the high expected number of false-positive findings. We are in the process of assembling a collection of RCC cases and controls from different studies to serve as a replication sample for this purpose. To assist in the replication of GWAS findings, we propose to identify, and extract DNA from, a nested case-control sample of approximately 300 RCC cases and 300 controls from within the PLCO Trial. The PLCO specimens will be pooled with Caucasian samples from the ATBC trial (225 cases, 750 controls), the ACS cohort (150 cases, 150 controls) and a U.S. case-control study of RCC recently completed by NCI (800 cases, 800 controls). The replication sample is expected to include 1,475 cases and 2,000 controls in total. The top ~25,000 SNPs from the primary scan will be genotyped in this replication sample using the Illumina iSelect® assay. Joint analyses of the primary and replication scans will have adequate power to detect per allele odds ratios of 1.3 or greater at a genome-wide significance level of 10-5.
Aims

The aim of this study is to select and extract DNA from a sample of 300 RCC cases and 300 controls within the PLCO Trial, in order to assist in the replication of GWAS findings. The PLCO specimens will contribute towards a pooled set of samples (1,475 cases, 2,000 controls) that will undergo genotyping for the top ~25,000 SNPs from the primary scan (317,000 SNPs) within the Eastern European case-control study of kidney cancer.

Collaborators

Stephen Chanock (NCI Core Genotyping Facility)
Nilanjan Chatterjee (NCI, DCEG)
Wong-Ho Chow (NCI, DCEG)
Kevin Jacobs (NCI Core Genotyping Facility)
Lee Moore (NCI, DCEG)
Mark Purdue (NCI, DCEG)
Mark Purdue (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
Meredith Yeager (NCI Core Genotyping Facility)

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