Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent

Chang, Bao‐Li; Spangler, Edward L.; Gallagher, Stephen; Haiman, Christopher A.; Henderson, Brian E.; Isaacs, William B.; Benford, Marnita L.; Kidd, LaCreis R.; Cooney, Kathleen A.; Strom, Sara S.; Ingles, Sue A.; Stern, Mariana C.; Corral, Román; Joshi, Amit D.; Xu, Jianfeng; Giri, Veda N.; Rybicki, Benjamin A.; Neslund‐Dudas, Christine; Kibel, Adam S.; Thompson, Ian M.; Leach, Robin J.; Ostrander, Elaine A.; Stanford, Janet L.; Witte, John S.; Casey, Graham; Eeles, Rosalind; Hsing, Ann W.; Chanock, Stephen J.; Hu, Jennifer J.; John, Esther M.; Park, Jong Y.; Stefflova, Klara; Zeigler‐Johnson, Charnita; Rebbeck, Timothy R.

doi:10.1158/1055-9965.epi-10-0698

Cited by 87 publications

(95 citation statements)

References 54 publications

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“…4,19 Other replication studies have also confirmed an association between rs10993994 and increased PCa risk. 18,20,21 Our observations (Table 3) suggest that increased PCa risk associated with the minor allele (T) of rs10993994 is probably inherited in a recessive manner. Taken together, these findings support further exploratory studies using rs10993994 as a predictive genetic marker of PCa susceptibility in programs such as targeted screening for PCa in high-risk individuals or personalized PCa risk assessment.…”

Section: Discussionmentioning

confidence: 82%

Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

Halley

Wei

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND: Both genetics and the environment are implicated as risk factors for prostate cancer (PCa). This populationbased case--control study evaluated four single-nucleotide polymorphisms (SNPs) previously identified by genome-wide association studies to be associated with increased PCa susceptibility. Potential relationships between serum concentrations of phyto-estrogens and SNPs were also investigated. METHODS: Four SNPs (rs10993994, rs2660753, rs1016343 and rs6983267) were genotyped in 247 PCa patients, 125 BPH patients and 274 control men recruited in Scotland. Serum concentrations of the phyto-estrogens enterolactone, equol, genistein and daidzein were measured by isotope dilution gas chromatography--mass spectrometry. RESULTS: Increased PCa risk was associated with TT genotype of rs10993994 compared with CC and CT genotypes combined (odds ratio (OR) ¼ 1.87; 95% confidence interval (CI), 1.26--2.77). TT homozygotes who had low serum enterolactone concentrations (below median) were more likely to have PCa (OR ¼ 2.90; 95% CI, 1.28--6.57) than individuals with CC/CT genotype and high serum enterolactone concentrations (above median). PCa was not associated with the other three SNPs tested. CONCLUSIONS: PCa susceptibility was associated with TT genotype of SNP rs10993994 in this cohort of Scottish men and the increased risk of PCa was modified by serum enterolactone concentrations.

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Section: Discussionmentioning

confidence: 82%

Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

Halley

Wei

et al. 2012

Prostate Cancer Prostatic Dis

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“…As of this writing, one PCa GWAS has been performed for each of African and Asian ancestries (8,9). Replication studies for variants discovered in European populations have also been performed in these populations (22)(23)(24)(25)(26)(27)(28). The 10q, 17q, and Xp variants (rs10993994, rs4430796, and rs5945619) are associated with PCa risk in men of European, Japanese, and African ancestries (8,(23)(24)(25), and these polymorphisms are also associated with MSMB, NCOA4, HNF1B, and NUDT11 transcripts across all three ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Genetic and functional analyses implicate the NUDT11 , HNF1B , and SLC22A3 genes in prostate cancer pathogenesis

Grisanzio¹,

Werner²,

Takeda

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

103

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One of the central goals of human genetics is to discover the genes and pathways driving human traits. To date, most of the common risk alleles discovered through genome-wide association studies (GWAS) map to nonprotein-coding regions. Because of our relatively poorer understanding of this part of the genome, the functional consequences of trait-associated variants pose a considerable challenge. To identify the genes through which risk loci act, we hypothesized that the risk variants are regulatory elements. For each of 12 known risk polymorphisms, we evaluated the correlation between risk allele status and transcript abundance for all annotated protein-coding transcripts within a 1-Mb interval. A total of 103 transcripts were evaluated in 662 prostate tissue samples [normal (n = 407) and tumor (n = 255)] from 483 individuals [European Americans (n = 233), Japanese (n = 127), and African Americans (n = 123)]. In a pooled analysis, 4 of the 12 risk variants were strongly associated with five transcripts (NUDT11, MSMB, NCOA4, SLC22A3, and HNF1B) in histologically normal tissue (P ≤ 0.001). Although associations were also observed in tumor tissue, they tended to be more attenuated. Previously, we showed that MSMB and NCOA4 participate in prostate cancer pathogenesis. Suppressing the expression of NUDT11, SLC22A3, and HNF1B influences cellular phenotypes associated with tumor-related properties in prostate cancer cells. Taken together, the data suggest that these transcripts contribute to prostate cancer pathogenesis.expression quantitative trait loci | prostate cancer risk SNPs | multi-ethnic

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“…Additional markers have been reported to be associated with prostate cancer at 8q24 particularly in men of African descent that were not originally identified in GWAS based in European populations. These include rs7008482 (11,14,16), rs4871005 (11,14), rs6981122 (11,14), and bd11934905 (21,26,51). These markers also hold promise for further study of clinical utility in prostate cancer risk assessment.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

Ishak

Giri

2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Several prostate cancer genome-wide association studies (GWAS) have identified riskassociated genetic variants primarily in populations of European descent. Less is known about the association of these variants in high-risk populations, including men of African descent and men with a family history of prostate cancer. This article provides a detailed review of published studies of prostate cancer-associated genetic variants originally identified in GWAS and replicated in high-risk populations.Methods: Articles replicating GWAS findings (National Human Genome Research Institute GWAS database) were identified by searching PubMed and relevant data were extracted.Results: Eleven replication studies were eligible for inclusion in this review. Of more than 30 singlenucleotide polymorphisms (SNP) identified in prostate cancer GWAS, 19 SNPs (63%) were replicated in men of African descent and 10 SNPs (33%) were replicated in men with familial and/or hereditary prostate cancer (FPC/HPC). The majority of SNPs were located at the 8q24 region with modest effect sizes (OR 1.11-2.63 in African American men and OR 1.3-2.51 in men with FPC). All replicated SNPs at 8q24 among men of African descent were within or near regions 2 and 3.Conclusions: This systematic review revealed several GWAS markers with replicated associations with prostate cancer in men of African descent and men with FPC/HPC. The 8q24 region continues to be the most implicated in prostate cancer risk. These replication data support ongoing study of clinical utility and potential function of these prostate cancer-associated variants in high-risk men.Impact: The replicated SNPs presented in this review hold promise for personalizing risk assessment for prostate cancer for high-risk men upon further study. Cancer Epidemiol Biomarkers Prev; 20(8); 1599-610. Ó2011 AACR.

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Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent

Cited by 87 publications

References 54 publications

Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

Genetic and functional analyses implicate the NUDT11 , HNF1B , and SLC22A3 genes in prostate cancer pathogenesis

A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

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