Dataset Information

GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP).

ABSTRACT: BACKGROUND:Genome-wide association studies (GWAS) have identified numerous common SNPs associated with prostate cancer (CaP) risk in men of European descent. This study evaluates GWAS SNPs associated with CaP in African Americans (AAs) and European Americans (EA). METHODS:Eight hundred SNPs were genotyped, including 32 from European-based GWAS and 35 flanking SNPs, in 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared to 925 AA and 1,687 EA controls from Illumina's iControlDB. The 32 GWAS SNPs were evaluated for their predictive power to discriminate between cases and controls using ROC curves. RESULTS:Of the 32 GWAS SNPs, 13 were significant at P?

SUBMITTER: Xu Z

PROVIDER: S-EPMC3403828 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP).

Xu Zongli Z Bensen Jeannette T JT Smith Gary J GJ Mohler James L JL Taylor Jack A JA

The Prostate 20101117 8

<h4>Background</h4>Genome-wide association studies (GWAS) have identified numerous common SNPs associated with prostate cancer (CaP) risk in men of European descent. This study evaluates GWAS SNPs associated with CaP in African Americans (AAs) and European Americans (EA).<h4>Methods</h4>Eight hundred SNPs were genotyped, including 32 from European-based GWAS and 35 flanking SNPs, in 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared to 925 AA and 1,687 EA controls ...[more]

PMID: 21456070

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Project description:Background: Moose ( Alces alces) colonized the North American continent from Asia less than 15,000 years ago, and spread across the boreal forest regions of Canada and the northern United States (US). Contemporary populations have low genetic diversity, due either to low number of individuals in the original migration (founder effect), and/or subsequent population bottlenecks in North America. Genetic tests based on informative single nucleotide polymorphism (SNP) markers are helpful in forensic and wildlife conservation activities, but have been difficult to develop for moose, due to the lack of a reference genome assembly and whole genome sequence (WGS) data. Methods: WGS data were generated for four individual moose from the US states of Alaska, Idaho, Wyoming, and Vermont with minimum and average genome coverage depths of 14- and 19-fold, respectively. Cattle and sheep reference genomes were used for aligning sequence reads and identifying moose SNPs. Results: Approximately 11% and 9% of moose WGS reads aligned to cattle and sheep genomes, respectively. The reads clustered at genomic segments, where sequence identity between these species was greater than 95%. In these segments, average mapped read depth was approximately 19-fold. Sets of 46,005 and 36,934 high-confidence SNPs were identified from cattle and sheep comparisons, respectively, with 773 and 552 of those having minor allele frequency of 0.5 and conserved flanking sequences in all three species. Among the four moose, heterozygosity and allele sharing of SNP genotypes were consistent with decreasing levels of moose genetic diversity from west to east. A minimum set of 317 SNPs, informative across all four moose, was selected as a resource for future SNP assay design. Conclusions: All SNPs and associated information are available, without restriction, to support development of SNP-based tests for animal identification, parentage determination, and estimating relatedness in North American moose.

Dataset Information

GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP).

Publications

GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP).

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