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

被引:17
作者
Irizarry-Ramirez, Margarita [1 ]
Kittles, Rick A. [2 ]
Wang, Xuemei [3 ]
Salgado-Montilla, Jeannette [4 ]
Nogueras-Gonzalez, Graciela M. [3 ]
Sanchez-Ortiz, Ricardo [5 ]
Guerrios, Lourdes [6 ]
Rivera, Keila [7 ]
Shah, Ebony [2 ]
Prokhorova, Ina [8 ]
Roberson, Pamela [9 ]
Troncoso, Patricia [8 ]
Pettaway, Curtis A. [9 ]
机构
[1] Univ Puerto Rico, Sch Hlth Profess, Clin Sci Lab, Dept Grad Studies, Med Sci Campus,Box 365067, San Juan, PR 00936 USA
[2] Univ Arizona, Sch Med, Dept Surg, Phoenix, AZ USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[4] Univ Puerto Rico, MD Anderson Canc Ctr Partnership Excellence Canc, Med Sci Campus, San Juan, PR 00936 USA
[5] Urol & Oncol Inst, San Juan, PR USA
[6] Vet Adm Caribbean Hlth Care Syst, San Juan, PR USA
[7] Univ Puerto Rico, Sch Med, Dept Pathol, Med Sci Campus, San Juan, PR 00936 USA
[8] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[9] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
comparative; hispanic; understudied; GENOME-WIDE ASSOCIATION; POPULATION-STRUCTURE; WEST-AFRICAN; RISK; 8Q24; LOCI; AGGRESSIVENESS; ADMIXTURE; INFERENCE; PATTERNS;
D O I
10.1002/pros.23368
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundThe 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. MethodsA 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 (GS7[3+4]), TSpT2) and high risk (GS7[4+3], TS>pT2) PCa. Statistical analyses were done using SAS. ResultsNo 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). ConclusionThe 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.
引用
收藏
页码:1118 / 1127
页数:10
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