BACKGROUND: Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry. METHODS: A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods. RESULTS: Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P=0.002). SNPs rs1561131 (genotypic, P=0.007), rs1963562 (dominant, P=0.01) and rs615382 (recessive, P=0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P=0.04) and rs1963562 (P=0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113-, rs1963562-rs615382l and rs1993973-rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P=0.032 and 0.0017, respectively). CONCLUSIONS: The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities.
BACKGROUND:Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry. METHODS: A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods. RESULTS: Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P=0.002). SNPs rs1561131 (genotypic, P=0.007), rs1963562 (dominant, P=0.01) and rs615382 (recessive, P=0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P=0.04) and rs1963562 (P=0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113-, rs1963562-rs615382l and rs1993973-rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P=0.032 and 0.0017, respectively). CONCLUSIONS: The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities.
Authors: Charnita Zeigler-Johnson; Tara Friebel; Amy H Walker; Yiting Wang; Elaine Spangler; Saarene Panossian; Margerie Patacsil; Richard Aplenc; Alan J Wein; S Bruce Malkowicz; Timothy R Rebbeck Journal: Cancer Res Date: 2004-11-15 Impact factor: 12.701
Authors: C Rodríguez; E E Calle; H L Miracle-McMahill; L M Tatham; P A Wingo; M J Thun; C W Heath Journal: Epidemiology Date: 1997-11 Impact factor: 4.822
Authors: Sarah J Plummer; David V Conti; Pamela L Paris; Anthony P Curran; Graham Casey; John S Witte Journal: Cancer Epidemiol Biomarkers Prev Date: 2003-09 Impact factor: 4.254
Authors: Karen H Lu; Andrea P Patterson; Lin Wang; Rebecca T Marquez; Edward N Atkinson; Keith A Baggerly; Lance R Ramoth; Daniel G Rosen; Jinsong Liu; Ingegerd Hellstrom; David Smith; Lynn Hartmann; David Fishman; Andrew Berchuck; Rosemarie Schmandt; Regina Whitaker; David M Gershenson; Gordon B Mills; Robert C Bast Journal: Clin Cancer Res Date: 2004-05-15 Impact factor: 12.531
Authors: Khadijah A Mitchell; Ebony Shah; Elise D Bowman; Adriana Zingone; Noah Nichols; Sharon R Pine; Rick A Kittles; Bríd M Ryan Journal: Cancer Causes Control Date: 2019-08-29 Impact factor: 2.506
Authors: Bradford D Wilson; Luisel J Ricks-Santi; Tshela E Mason; Muneer Abbas; Rick A Kittles; Georgia M Dunston; Yasmine M Kanaan Journal: Cancer Genomics Proteomics Date: 2018 May-Jun Impact factor: 4.069
Authors: Michael J Hall; Karen J Ruth; David Yt Chen; Laura M Gross; Veda N Giri Journal: Hered Cancer Clin Pract Date: 2015-04-08 Impact factor: 2.857
Authors: Julyann Pérez-Mayoral; Marievelisse Soto-Salgado; Ebony Shah; Rick Kittles; Mariana C Stern; Myrta I Olivera; María Gonzalez-Pons; Segundo Rodriguez-Quilichinni; Marla Torres; Jose S Reyes; Luis Tous; Nicolas López; Victor Carlo Chevere; Marcia Cruz-Correa Journal: Hum Genomics Date: 2019-02-20 Impact factor: 4.639