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Basic Research

Identification of genetic risk associated with prostate cancer using ancestry informative markers

Prostate Cancer and Prostatic Diseases volume 15, pages 359–364 (2012)Cite this article

Subjects

Abstract

Background:

Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry.

Methods:

A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods.

Results:

Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P=0.002). SNPs rs1561131 (genotypic, P=0.007), rs1963562 (dominant, P=0.01) and rs615382 (recessive, P=0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P=0.04) and rs1963562 (P=0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113–, rs1963562–rs615382l and rs1993973–rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P=0.032 and 0.0017, respectively).

Conclusions:

The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities.

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Acknowledgements

This project was supported in whole or in part with Federal funds from the National Center for Research Resources (NCRR) (UL1RR031975), National Institutes of health (NIH), through the Clinical and Translational Science Awards Program (CTSA), from the RCMI Program at Howard University (G12 RR003048), Division of Research Infrastructure, NCRR, NIH and the Howard University Cancer Center/Johns Hopkins Cancer Center Partnership (U54 CA091431), NCI, NIH.

Author contributions

LJR-S, VA, TM and GB participated in the design of the study, performed the statistical analysis and helped draft the manuscript. TM, BW, MA, WH, SH and MD carried out the molecular genetic studies, participated in SNP annotation, and helped draft the manuscript. CA, GD and RK conceived the study, participated in its design and coordination and helped to draft the manuscript.

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Authors and Affiliations

  1. Division of Genetics, Department of Pediatrics and Child Health, Howard University College of Medicine, Washington, DC, USA

    L J Ricks-Santi

  2. Department of Community and Family Medicine, National Human Genome Center at Howard University, Washington, DC, USA

    L J Ricks-Santi, V Apprey, T Mason, B Wilson, M Abbas, G Bonney & G Dunston

  3. College of Medicine, Howard University Cancer Center, Washington, DC, USA

    L J Ricks-Santi

  4. Department of Microbiology, Howard University College of Medicine, Washington, DC, USA

    M Abbas & G Dunston

  5. Department of Medicine, Committee on Cancer Biology, University of Chicago, Chicago, IL, USA

    W Hernandez

  6. Department of Medicine, University of Chicago, Chicago, IL, USA

    S Hooker

  7. Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA

    M Doura

  8. Division of Biological Sciences, Department of Medicine, The University of Chicago, Chicago, IL, USA

    R Kittles

  9. Department of Urology, Howard University College of Medicine, Washington, DC, USA

    C Ahaghotu

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  1. L J Ricks-Santi
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Correspondence to L J Ricks-Santi.

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Ricks-Santi, L., Apprey, V., Mason, T. et al. Identification of genetic risk associated with prostate cancer using ancestry informative markers. Prostate Cancer Prostatic Dis 15, 359–364 (2012). https://doi.org/10.1038/pcan.2012.19

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