Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans

Christopher A. Haiman, Gary K. Chen, William J. Blot, Sara S. Strom, Sonja I. Berndt, Rick A Kittles, Benjamin A. Rybicki, William B. Isaacs, Sue A. Ingles, Janet L. Stanford, W. Ryan Diver, John S. Witte, Stephen J. Chanock, Suzanne Kolb, Lisa B. Signorello, Yuko Yamamura, Christine Neslund-Dudas, Michael J. Thun, Adam Murphy, Graham CaseyXin Sheng, Peggy Wan, Loreall C. Pooler, Kristine R. Monroe, Kevin M. Waters, Loic Le Marchand, Laurence N. Kolonel, Daniel O. Stram, Brian E. Henderson

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 African Americans. At 8q24, we found 9 variants (p≤6×10-4) that best capture risk of prostate cancer in African Americans, 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 African Americans (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 African Americans. 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.

Original languageEnglish (US)
Article numbere1001387
JournalPLoS Genetics
Volume7
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

Fingerprint

African American
prostatic neoplasms
African Americans
cancer
Prostatic Neoplasms
loci
Genome-Wide Association Study
allele
Alleles
alleles
etiology
ethnic group
ancestry
nationalities and ethnic groups
Ethnic Groups
genomics
risk factors
marker
modeling

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Haiman, C. A., Chen, G. K., Blot, W. J., Strom, S. S., Berndt, S. I., Kittles, R. A., ... Henderson, B. E. (2011). Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans. PLoS Genetics, 7(5), [e1001387]. https://doi.org/10.1371/journal.pgen.1001387

Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans. / 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.

In: PLoS Genetics, Vol. 7, No. 5, e1001387, 05.2011.

Research output: Contribution to journalArticle

Haiman, CA, Chen, GK, Blot, WJ, Strom, SS, Berndt, SI, Kittles, RA, Rybicki, BA, Isaacs, WB, Ingles, SA, Stanford, JL, Diver, WR, Witte, JS, Chanock, SJ, Kolb, S, Signorello, LB, Yamamura, Y, Neslund-Dudas, C, Thun, MJ, Murphy, A, Casey, G, Sheng, X, Wan, P, Pooler, LC, Monroe, KR, Waters, KM, Le Marchand, L, Kolonel, LN, Stram, DO & Henderson, BE 2011, 'Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans', PLoS Genetics, vol. 7, no. 5, e1001387. https://doi.org/10.1371/journal.pgen.1001387
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. / Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans. In: PLoS Genetics. 2011 ; Vol. 7, No. 5.
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AU - Rybicki, Benjamin A.

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AU - Neslund-Dudas, Christine

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AU - Casey, Graham

AU - Sheng, Xin

AU - Wan, Peggy

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AU - Waters, Kevin M.

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