A genome-wide association study of prostate cancer in Latinos

Zhaohui Du, Hannah Hopp, Sue A. Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Thomas J. Hoffmann, Esther M. John, Stephen K. Van Den Eeden, Sara Strom, Robin J Leach, Ian M. Thompson, John S. Witte, David V. Conti, Christopher A. Haiman

Research output: Contribution to journalArticle

Abstract

Latinos represent <1% of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men. We also conducted a genetic admixture-mapping scan to identify PrCa risk alleles associated with local ancestry. Genome-wide significant associations were observed with 84 variants all located at the known PrCa risk regions at 8q24 (128.484–128.548) and 10q11.22 (MSMB gene). In admixture mapping, we observed genome-wide significant associations with local African ancestry at 8q24. Of the 162 established PrCa risk variants that are common in Latino men, 135 (83.3%) had effects that were directionally consistent as previously reported, among which 55 (34.0%) were statistically significant with p < 0.05. A polygenic risk model of the known PrCa risk variants showed that, compared to men with average risk (25th–75th percentile of the polygenic risk score distribution), men in the top 10% had a 3.19-fold (95% CI: 2.65, 3.84) increased PrCa risk. In conclusion, we found that the known PrCa risk variants can effectively stratify PrCa risk in Latino men. Larger studies in Latino populations will be required to discover and characterize genetic risk variants for PrCa and improve risk stratification for this population.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Genome-Wide Association Study
Hispanic Americans
Prostatic Neoplasms
Population
Genome
Precision Medicine

Keywords

  • admixture mapping
  • GWAS
  • Latino men
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Du, Z., Hopp, H., Ingles, S. A., Huff, C., Sheng, X., Weaver, B., ... Haiman, C. A. (Accepted/In press). A genome-wide association study of prostate cancer in Latinos. International Journal of Cancer. https://doi.org/10.1002/ijc.32525

A genome-wide association study of prostate cancer in Latinos. / Du, Zhaohui; Hopp, Hannah; Ingles, Sue A.; Huff, Chad; Sheng, Xin; Weaver, Brandi; Stern, Mariana; Hoffmann, Thomas J.; John, Esther M.; Van Den Eeden, Stephen K.; Strom, Sara; Leach, Robin J; Thompson, Ian M.; Witte, John S.; Conti, David V.; Haiman, Christopher A.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Du, Z, Hopp, H, Ingles, SA, Huff, C, Sheng, X, Weaver, B, Stern, M, Hoffmann, TJ, John, EM, Van Den Eeden, SK, Strom, S, Leach, RJ, Thompson, IM, Witte, JS, Conti, DV & Haiman, CA 2019, 'A genome-wide association study of prostate cancer in Latinos', International Journal of Cancer. https://doi.org/10.1002/ijc.32525
Du, Zhaohui ; Hopp, Hannah ; Ingles, Sue A. ; Huff, Chad ; Sheng, Xin ; Weaver, Brandi ; Stern, Mariana ; Hoffmann, Thomas J. ; John, Esther M. ; Van Den Eeden, Stephen K. ; Strom, Sara ; Leach, Robin J ; Thompson, Ian M. ; Witte, John S. ; Conti, David V. ; Haiman, Christopher A. / A genome-wide association study of prostate cancer in Latinos. In: International Journal of Cancer. 2019.
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abstract = "Latinos represent <1{\%} of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men. We also conducted a genetic admixture-mapping scan to identify PrCa risk alleles associated with local ancestry. Genome-wide significant associations were observed with 84 variants all located at the known PrCa risk regions at 8q24 (128.484–128.548) and 10q11.22 (MSMB gene). In admixture mapping, we observed genome-wide significant associations with local African ancestry at 8q24. Of the 162 established PrCa risk variants that are common in Latino men, 135 (83.3{\%}) had effects that were directionally consistent as previously reported, among which 55 (34.0{\%}) were statistically significant with p < 0.05. A polygenic risk model of the known PrCa risk variants showed that, compared to men with average risk (25th–75th percentile of the polygenic risk score distribution), men in the top 10{\%} had a 3.19-fold (95{\%} CI: 2.65, 3.84) increased PrCa risk. In conclusion, we found that the known PrCa risk variants can effectively stratify PrCa risk in Latino men. Larger studies in Latino populations will be required to discover and characterize genetic risk variants for PrCa and improve risk stratification for this population.",
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AU - Huff, Chad

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AU - Weaver, Brandi

AU - Stern, Mariana

AU - Hoffmann, Thomas J.

AU - John, Esther M.

AU - Van Den Eeden, Stephen K.

AU - Strom, Sara

AU - Leach, Robin J

AU - Thompson, Ian M.

AU - Witte, John S.

AU - Conti, David V.

AU - Haiman, Christopher A.

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