Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans

Authors

  • Jeannette T. Bensen,

    1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Zongli Xu,

    1. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
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  • Gary J. Smith,

    1. Department of Urology, Roswell Park Cancer Institute, Buffalo, New York
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  • James L. Mohler,

    1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    2. Department of Urology, Roswell Park Cancer Institute, Buffalo, New York
    3. Department of Urology, University of Buffalo School of Medicine and Biotechnology, Buffalo, New York
    4. Department of Surgery, Division of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Elizabeth T.H. Fontham,

    1. Louisiana State University Health Sciences Center School of Public Health, New Orleans, Louisiana
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  • Jack A. Taylor

    Corresponding author
    1. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
    2. Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
    • National Institute of Environmental Health Sciences, MD A3-05, 111 TW Alexander Dr., PO Box 12233, Research Triangle Park, NC 27709.
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  • First authorship shared by Dr. Bensen and Dr. Xu.

  • Conflicts of interset: None.

Abstract

BACKGROUND

Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men.

METHODS

A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable.

RESULTS

Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and seven flanking SNPs were associated with CaP aggressiveness (P < 0.05) in three genomic regions: One at 3p12 (EA), seven at 8q24 (5 AA, 2 EA), and three at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (two AA, one AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (P < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons.

CONCLUSIONS

Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. Prostate 73: 11–22, 2013. © 2012 Wiley Periodicals, Inc.

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