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A genome-wide association study of prostate cancer in West African men

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An Erratum to this article was published on 03 December 2013

Abstract

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E−7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E−8), and SNPs at Xq28 (rs985081, p = 8.66E−9) and 6q21 (rs2185710, p = 5.95E−8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.

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Notes

  1. http://www.cdc.gov/features/canceratlas/.

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Acknowledgments

The authors thank Ms. Vicky Okyne for her expert help in coordinating the study; consultants/resident urologists, pathologists, nurses, and interviewers of Korle‐Bu Hospital and University of Ghana Medical School for their assistance with subject enrollment, screening, and clinical examination; the study participants for their contribution toward a better understanding of prostate disease; A. DeMarzo and G. Netto of Johns Hopkins University for pathology review; Ms. Violet Devairakkam, Ms. Norma Kim, and Mr. John Heinrich of Research Triangle Institute (RTI) for their expert study management; Prof. Rosalind A. Eeles and her team for cross-checking published prostate cancer loci specified in Table 3; and members of the African Ancestry Prostate Cancer GWAS Consortium for looking-up our most promising associations from our African GWAS. This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services including Contract No. HHSN261200800001E.

Conflict of interest

There are no financial disclosures from any of the authors.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 9609 Medical Center Drive, Rm 7-E106, MSC 9774, Bethesda, MD, 20892-9774, USA

    Michael Blaise Cook, Zhaoming Wang, Charles C. Chung, Meredith Yeager, Amy Hutchinson, Kai Yu, Robert N. Hoover & Stephen J. Chanock

  2. Cancer Genomics Research Laboratory, NCI-DCEG, SAIC-Frederick Inc, Frederick, MD, USA

    Zhaoming Wang, Meredith Yeager & Amy Hutchinson

  3. Korle Bu Teaching Hospital, PO Box 77, Accra, Ghana

    Edward D. Yeboah, Yao Tettey, Richard B. Biritwum, Andrew A. Adjei & Evelyn Tay

  4. University of Ghana Medical School, PO Box 4236, Accra, Ghana

    Edward D. Yeboah, Yao Tettey, Richard B. Biritwum, Andrew A. Adjei & Evelyn Tay

  5. Westat, 1600 Research Boulevard, Rockville, MD, 20850-3129, USA

    Ann Truelove & Shelley Niwa

  6. School of Public Health, University of California, Berkeley, CA, USA

    Annand P. Chokkalingam & Ann W. Hsing

  7. Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA, 94538, USA

    Lisa W. Chu

  8. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Kristin A. Rand & Christopher A. Haiman

  9. Stanford Cancer Institute, Stanford University, 875 Blake Wilbur Drive Stanford, Stanford, CA, 94305, USA

    Ann W. Hsing

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  1. Michael Blaise Cook
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  19. Ann W. Hsing
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  20. Stephen J. Chanock
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African Ancestry Prostate Cancer GWAS Consortium

Corresponding author

Correspondence to Michael Blaise Cook.

Additional information

M. B. Cook, Z. Wang and E. D. Yeboah are co-first authors.

A. W. Hsing and S. J. Chanock are co-last authors.

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Cook, M.B., Wang, Z., Yeboah, E.D. et al. A genome-wide association study of prostate cancer in West African men. Hum Genet 133, 509–521 (2014). https://doi.org/10.1007/s00439-013-1387-z

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  • DOI: https://doi.org/10.1007/s00439-013-1387-z

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