Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese. Nat Genet 44(426-9):S1

Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
Nature Genetics (Impact Factor: 29.35). 02/2012; 44(4):426-9, S1. DOI: 10.1038/ng.1104
Source: PubMed


We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.

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Available from: Takahiko Katoh, Apr 16, 2014
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    • "As of October 2012, a total of 94 single nucleotide polymorphisms (SNPs) across 41 chromosomal loci were reported to achieve a genome-wide significance level, which we conservatively define in this report as a p-value < 10-6 in order to maximize capture of potential loci, across 18 GWAS (Figure 1 and Additional file 1: Table S1). Of the 18 GWAS, a total of 15 (83%) were performed within a European (including one Latin American [15]) study population, two on a Japanese cohort [16,17] and a single GWAS has exclusively targeted African American’s [18]. "
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    ABSTRACT: Although African ancestry represents a significant risk factor for prostate cancer, few studies have investigated the significance of prostate cancer and relevance of previously defined genetic and epidemiological prostate cancer risk factors within Africa. We recently established the Southern African Prostate Cancer Study (SAPCS), a resource for epidemiological and genetic analysis of prostate cancer risk and outcomes in Black men from South Africa. Biased towards highly aggressive prostate cancer disease, this is the first reported data analysis. The SAPCS is an ongoing population-based study of Black men with or without prostate cancer. Pilot analysis was performed for the first 837 participants, 522 cases and 315 controls. We investigate 46 pre-defined prostate cancer risk alleles and up to 24 epidemiological measures including demographic, lifestyle and environmental factors, for power to predict disease status and to drive on-going SAPCS recruitment, sampling procedures and research direction. Preliminary results suggest that no previously defined risk alleles significantly predict prostate cancer occurrence within the SAPCS. Furthermore, genetic risk profiles did not enhance the predictive power of prostate specific antigen (PSA) testing. Our study supports several lifestyle/environmental factors contributing to prostate cancer risk including a family history of cancer, diabetes, current sexual activity and erectile dysfunction, balding pattern, frequent aspirin usage and high PSA levels. Despite a clear increased prostate cancer risk associated with an African ancestry, experimental data is lacking within Africa. This pilot study is therefore a significant contribution to the field. While genetic risk factors (largely European-defined) show no evidence for disease prediction in the SAPCS, several epidemiological factors were associated with prostate cancer status. We call for improved study power by building on the SAPCS resource, further validation of associated factors in independent African-based resources, and genome-wide approaches to define African-specific risk alleles.
    BMC Urology 12/2013; 13(1):74. DOI:10.1186/1471-2490-13-74 · 1.41 Impact Factor
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    • "A recent GWAS PCa study identified rs2252004 at 10q26 to be significantly associated with PCa risk at a genome-wide significant level (P = 1.98E − 8) in the Japanese population [11]. It was further confirmed to contribute to PCa risk in a Chinese population [12]. "
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    ABSTRACT: Recent studies reported that rs2252004 at 10q26 was significantly associated with prostate cancer (PCa) risk in a Japanese population and was subsequently confirmed in a Chinese population. We aimed to assess the relationship between this locus and risk/aggressiveness of benign prostatic hyperplasia (BPH). The current study included 426 BPH cases and 1,008 controls from Xinhua Hospital in Shanghai, China. All BPH patients were treated with α -adrenergic blockers and 5 α -reductase inhibitors for at least 9 months. Associations between rs2252004 and BPH risk/aggressiveness were tested using logistic regression. Associations between rs2252004 and clinical parameters including International Prostate Symptom Score (IPSS), total prostate volume (TPV), total PSA (tPSA), and free PSA (fPSA) were evaluated by linear regression. Allele "A" in rs2252004 was significantly associated with increased risk for aggressiveness of BPH in a Chinese population (OR = 1.42, 95% CI: 1.04-1.96, P = 0.03). Patients with the genotype "A/A" (homozygous minor allele) had an increase of IPSS and TPV after treatment (P = 0.045 and 0.024, resp.). No association was observed between rs2252004, BPH risk, and baseline clinicopathological traits (All P > 0.05). Our study is the first to show that rs2252004 at 10q26 was associated with BPH aggressiveness and efficacy of BPH treatment.
    Biochemistry Research International 08/2013; 2013(1):820849. DOI:10.1155/2013/820849
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    • "Today GWAS have been remarkably successful in identifying dozens of common genetic variants or loci associated with PCa [239] [240] [241]. Most of those PCa predisposition SNP loci were initially identified in Western populations and half of them are not associated with PCa risk in the East Asian population [239] [240]. Two SNPs located at chromosome 4 have also been reported to show specific ethnical association with PCa risk [242]: rs12500426, which exhibited an association in Europeans but not in Asian or African American men and rs7679673, which was associated with disease in European and Asian populations but not in African American men. "
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    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 04/2013; 3(2):127-151. · 4.17 Impact Factor
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