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.

Download full-text


Available from: Robert Steen, Aug 14, 2015
  • Source
    • "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) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Knowledge from human genetic research continuously challenges the notion that race and biology are inextricably linked, with implications across biomedical and public health disciplines. However, biomedical research continues to explore health and disease under a racial framework ignoring and at times confounding the identification of true biological and/or environmental risk factors. Within this article, we present a brief overview of the use of race in biomedical research and studies of human genome variation and how genetic ancestry may help us understand health disparities. We believe that the casual use of “race” to define groups in biomedical research has contributed to our limited understanding of complex disease etiology and risk factors driving health disparities.
    Race and Social Problems 06/2013; 5(2). DOI:10.1007/s12552-013-9094-x
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second biggest cause of cancer death in men of the Western world. Higher incidences of PCa occur in men from North America, Oceania and Western countries, whereas men from Asia and North Africa have a much lower PCa incidence rate. Investigations into this population disparity of PCa incidence, in order to identify potential preventive factors or targets for the therapeutic intervention of PCa, have found differences in both environmental and genetic variations between these populations. Environmental variations include both diet and lifestyle, which vary widely between populations. Evidence that diet comes into play has been shown by men who immigrate from Eastern to Western countries. PCa incidence in these men is higher than men in their native countries. However the number of immigrants developing PCa still doesn't match native black/white men, therefore genetic factors also contribute to PCa risk, which are supported by familial studies. There are a number of genetic polymorphisms that are differentially presented between Western and Eastern men, which are potentially associated with PCa incidence. Androgen and its receptor (AR) play a major role in PCa development and progression. In this study, we focus on genes involved in androgen biosynthesis and metabolism, as well as those associated with AR pathway, whose polymorphisms affect androgen level and biological or physiological functions of androgen. While many of the genetic polymorphisms in this androgen/AR system showed different frequencies between populations, contradictory evidences exist for most of these genes investigated individually as to the true contribution to PCa risk. More accurate measurements of androgen activity within the prostate are required and further studies need to include more African and Asian subjects. As many of these genetic polymorphisms may contribute to different steps in the same biological/physiological function of androgen and AR pathway, an integrated analysis considering the combined effect of all the genetic polymorphisms may be necessary to assess their contribution to PCa initiation and progression.
    American Journal of Cancer Research 01/2013; 3(2):127-151. · 3.97 Impact Factor
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent study, which included meta-analysis of two genome-wide association studies (GWAS), followed by a replication, identified the association between single nucleotide polymorphism (SNP) rs3787016 at 19p13 and prostate cancer (PCa) risk. Considering possible genetic differences between populations, we conducted the study in order to evaluate the association of this polymorphism with prostate cancer risk in Serbian population. 261 samples of peripheral blood were obtained from the patients with PCa and 257 samples from patients with benign prostatic hyperplasia (BPH). 106 volunteers who gave samples of bucal swabs comprised the control group. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen (PSA) level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotypization of rs3787016 was performed by using Taqman(®) SNP Genotyping Assay. The differences in alelle and genotype frequencies between analyzed groups of subjects were performed by using PLINK, SPSS 17.0 for Windows and SNPStats statistical software. No significant association of rs3787016 with PCa risk was determined comparing allele and genotype frequencies among group of patients diagnosed with PCa and the control group, as well as among groups of patients with PCa and BPH. Also, no evidence of association of rs3787016 with PCa risk was shown using tests for association under dominant and recessive genetic models. SNP rs3787016 showed no significant association with standard prognostic parameters regarding PCa progression, nor with the risk of disease progression assessed according to two different risk classification systems.
    International Journal of Clinical and Experimental Medicine 01/2013; 6(1):57-66. · 1.42 Impact Factor
Show more