Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men

Margarita Irizarry-Ramírez, Rick A Kittles, Xuemei Wang, Jeannette Salgado-Montilla, Graciela M. Nogueras-González, Ricardo Sánchez-Ortiz, Lourdes Guerrios, Keila Rivera, Ebony Shah, Ina Prokhorova, Pamela Roberson, Patricia Troncoso, Curtis A. Pettaway

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. Methods: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA<2.5ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS≤7[3+4]), TS≤pT2) and high risk (GS≥7[4+3], TS>pT2) PCa. Statistical analyses were done using SAS. Results: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P<0.0001) and PR (P=0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P=0.034). Conclusion: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

Original languageEnglish (US)
JournalProstate
DOIs
StateAccepted/In press - 2017

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African Americans
Single Nucleotide Polymorphism
Prostatic Neoplasms
Alleles
Population
Passive Cutaneous Anaphylaxis
Neoplasm Grading
Case-Control Studies
Chromosomes
Phenotype
Mortality
Serum

Keywords

  • Comparative
  • Hispanic
  • Understudied

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Irizarry-Ramírez, M., Kittles, R. A., Wang, X., Salgado-Montilla, J., Nogueras-González, G. M., Sánchez-Ortiz, R., ... Pettaway, C. A. (Accepted/In press). Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men. Prostate. https://doi.org/10.1002/pros.23368

Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men. / Irizarry-Ramírez, Margarita; Kittles, Rick A; Wang, Xuemei; Salgado-Montilla, Jeannette; Nogueras-González, Graciela M.; Sánchez-Ortiz, Ricardo; Guerrios, Lourdes; Rivera, Keila; Shah, Ebony; Prokhorova, Ina; Roberson, Pamela; Troncoso, Patricia; Pettaway, Curtis A.

In: Prostate, 2017.

Research output: Contribution to journalArticle

Irizarry-Ramírez, M, Kittles, RA, Wang, X, Salgado-Montilla, J, Nogueras-González, GM, Sánchez-Ortiz, R, Guerrios, L, Rivera, K, Shah, E, Prokhorova, I, Roberson, P, Troncoso, P & Pettaway, CA 2017, 'Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men', Prostate. https://doi.org/10.1002/pros.23368
Irizarry-Ramírez M, Kittles RA, Wang X, Salgado-Montilla J, Nogueras-González GM, Sánchez-Ortiz R et al. Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men. Prostate. 2017. https://doi.org/10.1002/pros.23368
Irizarry-Ramírez, Margarita ; Kittles, Rick A ; Wang, Xuemei ; Salgado-Montilla, Jeannette ; Nogueras-González, Graciela M. ; Sánchez-Ortiz, Ricardo ; Guerrios, Lourdes ; Rivera, Keila ; Shah, Ebony ; Prokhorova, Ina ; Roberson, Pamela ; Troncoso, Patricia ; Pettaway, Curtis A. / Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men. In: Prostate. 2017.
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abstract = "Background: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. Methods: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA<2.5ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS≤7[3+4]), TS≤pT2) and high risk (GS≥7[4+3], TS>pT2) PCa. Statistical analyses were done using SAS. Results: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P<0.0001) and PR (P=0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39{\%} vs 29{\%}, P=0.034). Conclusion: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.",
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AU - Kittles, Rick A

AU - Wang, Xuemei

AU - Salgado-Montilla, Jeannette

AU - Nogueras-González, Graciela M.

AU - Sánchez-Ortiz, Ricardo

AU - Guerrios, Lourdes

AU - Rivera, Keila

AU - Shah, Ebony

AU - Prokhorova, Ina

AU - Roberson, Pamela

AU - Troncoso, Patricia

AU - Pettaway, Curtis A.

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N2 - Background: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. Methods: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA<2.5ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS≤7[3+4]), TS≤pT2) and high risk (GS≥7[4+3], TS>pT2) PCa. Statistical analyses were done using SAS. Results: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P<0.0001) and PR (P=0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P=0.034). Conclusion: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

AB - Background: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. Methods: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA<2.5ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS≤7[3+4]), TS≤pT2) and high risk (GS≥7[4+3], TS>pT2) PCa. Statistical analyses were done using SAS. Results: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P<0.0001) and PR (P=0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P=0.034). Conclusion: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

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