Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in Black or African American

Details

• Alternative Title:
  PLoS Genet
• Personal Author:
  Haiman, Christopher A. ; Chen, Gary K. ; Blot, William J. ; Strom, Sara S. ; Berndt, Sonja I. ; Kittles, Rick A. ; Rybicki, Benjamin A. ; Isaacs, William B. ; Ingles, Sue A. ; Stanford, Janet L. ; Diver, W. Ryan ; Witte, John S. ; Chanock, Stephen J. ; Kolb, Suzanne ; Signorello, Lisa B. ; Yamamura, Yuko ; Neslund-Dudas, Christine ; Thun, Michael J. ; Murphy, Adam ; Casey, Graham ; Sheng, Xin ; Wan, Peggy ; Pooler, Loreall C. ; Monroe, Kristine R. ; Waters, Kevin M. ; Le Marchand, Loic ; Kolonel, Laurence N. ; Stram, Daniel O. ; Henderson, Brian E.
• Description:
  GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in Black or African American. At 8q24, we found 9 variants (p≤6×10(-4)) that best capture risk of prostate cancer in Black or African American, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in Black or African American (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in Black or African American. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.
• Subjects:
  Adult Aged Aged, 80 And Over Black Or African American Case-Control Studies Chromosomes, Human, Pair 8 Cohort Studies Gene Frequency Genetic Loci Genome-Wide Association Study Genotype Humans Linkage Disequilibrium Male Middle Aged Polymorphism, Single Nucleotide Prostatic Neoplasms White Young Adult

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• Source:
  PLoS Genet. 2011; 7(5).
• Pubmed ID:
  21637779
• Pubmed Central ID:
  PMC3102736
• Document Type:
  Journal Article
• Funding:
  1U58DP000807-3/DP/NCCDPHP CDC HHS/United States ; CA092447/CA/NCI NIH HHS/United States ; CA1326792/CA/NCI NIH HHS/United States ; CA148085/CA/NCI NIH HHS/United States ; CA54281/CA/NCI NIH HHS/United States ; CA63464/CA/NCI NIH HHS/United States ; CA88164/CA/NCI NIH HHS/United States ; ES011126/ES/NIEHS NIH HHS/United States ; HG004726/HG/NHGRI NIH HHS/United States ; N01-PC-35139/PC/NCI NIH HHS/United States ; P30 CA68485/CA/NCI NIH HHS/United States ; P50-CA140388/CA/NCI NIH HHS/United States ; R01 CA056678/CA/NCI NIH HHS/United States ; R01 CA082664/CA/NCI NIH HHS/United States ; R01 CA092447/CA/NCI NIH HHS/United States ; R01 CA092579/CA/NCI NIH HHS/United States ; R01CA68578/CA/NCI NIH HHS/United States ; S06GM08016/GM/NIGMS NIH HHS/United States
• Volume:
  7
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9dd0eb150d04990f33a3455a019196ec46d8c6ea292fa56a60ce75f452baf116
• Download URL:
  https://stacks.cdc.gov/view/cdc/22825/cdc_22825_DS1.pdf
• File Type:
  [PDF - 401.98 KB ]