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Freedman, M. et al. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc. Natl. Acad. Sci. USA 103, 14068-14073

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 09/2006; 103(38):14068-73. DOI: 10.1073/pnas.0605832103
Source: PubMed

ABSTRACT A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 x 10(-9)) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.

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    • "Table 1 Successful admixture mapping studies in African Americans Disease phenotype Disease locus References BMI Xq25 Cheng et al. (2009) Hypertension 6p21.1 Cheng et al. (2010) Interleukin 6 soluble receptor levels 1 Reich et al. (2007) Lung cancer (non-smallcell lung cancer) 1q42.13 Schwartz et al. (2011) Multiple sclerosis 1 Reich et al. (2005) Nondiabetic end-stage renal disease (ESRD) 22 Kao et al. (2008) Prostate cancer (\age 72) 8q24 Freedman et al. (2006) "
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    • "With the development of SNP array technology, a genome wide association study (GWAS) emerged for identifying small and moderate risk SNPs. The first two GWAS studies identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to PCa in 2006 [237] [238]. Today GWAS have been remarkably successful in identifying dozens of common genetic variants or loci associated with PCa [239] [240] [241]. "
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    • "GWAS have yielded a large number of PCa risk loci, currently more than 30, located at 2p15, 3p12, 6q25, 7p15, 7q21, 8q24, 10q11, 10q26, 11q13, 12q13, 17q12, 17q24, 19q13, and Xp11 [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]. Studies have also shown association of several risk alleles with clinical and pathological parameters of PCa, such as Gleason score, serum prostate-specific antigen "
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