Association Between Two Unlinked Loci at 8q24 and Prostate Cancer Risk Among European Americans

Zheng, S. Lilly; Sun, Jielin; Cheng, Yu Ching; Li, Ge; Hsu, Fang Chi; Zhu, Yi; Chang, Bao Li; Liu, Wennuan; Kim, Jin Woo; Turner, Aubrey R.; Gielzak, Marta; Yan, Guifang; Isaacs, Sarah D.; Wiley, Kathleen E.; Sauvageot, Jurga; Chen, Huann-Sheng; Gurganus, Robin; Mangold, Leslie A.; Trock, Bruce J.; Grönberg, Henrik; Duggan, David; Carpten, John D.; Partin, Alan W.; Walsh, Patrick C.; Xu, Jianfeng; Isaacs, William B.

doi:10.1093/jnci/djm169

Cited by 122 publications

(96 citation statements)

References 18 publications

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“…After further evaluation, we found only 24 casecontrol studies from 19 articles that were suitable for our meta-analysis of rs6983267 (Haiman et al, 2007;Yeager et al, 2007;Zheng et al, 2007;Cheng et al, 2008;Salinas et al, 2008;Terada et al, 2008;Wokolorczyk et al, 2008;Beuten et al, 2009;Liu et al, 2009;Penney et al, 2009;Zheng et al, 2009;Liu et al, 2011;Papanikolopoulou et al, 2011;Joung et al, 2012;Brankovic et al, 2013;Ho et al, 2013;Chan et al, 2013;Zhao et al, 2013;Oskina et al, 2014). Among these, 16 studies included populations of European descent and 8 included populations of Asian descent.…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

“…Subsequently, multiple independent studies have provided compelling evidence that has demonstrated that the risk of PCa is influenced by genetic variations in the 8q24 region (Haiman et al, 2007;Cheng et al, 2008). One promoter polymorphism rs6983267 T/G in the 8q24 region has been reported in genome-wide association studies (GWAS) to be significantly associated with PCa risk (Yeager et al, 2007;Zheng et al, 2007). While there have been numerous studies that have investigated associations between this polymorphism and the risk of PCa, the results have been inconsistent and inconclusive.…”

Section: Introductionmentioning

confidence: 99%

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Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis

Zhu

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Recent studies have indicated that single nucleotide polymorphisms (SNPs) within the 8q24 region may be a risk factor for prostate cancer (PCa). Here, we performed a meta-analysis to evaluate the association between the 8q24 rs6983267 T/G polymorphism and PCa risk. A systematic literature search was carried out in multiple electronic databases independently by two investigators. Pooled odds ratios (ORs) and 95% confidence intervals for 8q24 rs6983267 T/G and PCa were calculated using a fixed-effect model (the Mantel-Haenszel method). In total, 24 case-control studies from 19 articles were included in our meta-analysis. Our analysis indicated that there is a significant PCa risk associated with the rs6983267 polymorphism in a dominant model (GG vs GT+TT, pooled OR = 1.298, P < 0.001); recessive model (GG+GT vs TT, pooled OR = 1.302, P < 0.001); and homozygote comparison (GG vs TT, pooled OR = 1.494, P < 0.001). Similarly, in a subgroup analysis of European and Asian descent, our results revealed that there are associations between 19329-19341 (2015) rs6983267 T/G polymorphism and PCa susceptibility with the dominant model (GG vs GT+TT), recessive model (GG+GT vs TT), and homozygote comparison (GG vs TT). To investigate the association between rs6983267 and risk of PCa under different clinical conditions, further analyses were conducted regarding different clinical characteristics including the Gleason score, tumor stage, and PSA level to provide a more comprehensive view of PCa risk and this SNP. Publication bias was assed using the Begg test and the Egger test, and none was detected.

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Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis

Zhu

et al. 2015

Genet. Mol. Res.

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“…More recent studies using genomewide analyses have identified risk loci comprising SNPs on chromosome 8q24 and 17p to be associated with PCA (9)(10)(11)(12)(13)(14). How such polymorphisms affect the growth of PCA or the regulation of androgens, however, is inadequately addressed in the abovementioned genomewide studies.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer

Setlur

Chen

Hossain

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk.Experimental Design: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk. We also investigated associations between SNPs in genes (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT, and in DHT metabolism and PCA risk. The population consisted of 426 men (205 controls and 221 cases) who underwent prostate-specific antigen screening as part of a PCA early detection program in Tyrol, Austria.Results: No association between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95% confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13). Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when compared with men carrying neither (P = 0.005). Controls with the AA genotype on rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03).Conclusions: This is the first study to implicate the 5α-reductase isoform 1 (SRD5A1) and PCA risk, supporting the rationale of blocking enzymatic activity of both isoforms of 5α-reductase for PCA chemoprevention.

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“…Expression arrays, SNP analyses and mass spectrometry are new tools for biomarker identification (Zheng et al, 2007). Such high-throughput analyses have recently identified new prostate cancer biomarkers, including, for example, HEPSIN, EZH2 and a-methyl-Co-racemase (AMACR) (Dhanasekaran et al, 2001;Jiang et al, 2001;Luo et al, 2001;Magee et al, 2001;Stamey et al, 2001;Varambally et al, 2002;Rhodes et al, 2003;Parekh et al, 2007).…”

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confidence: 99%

GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics

et al. 2008

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GOLPH2 is coding the 73-kDa type II Golgi membrane antigen GOLPH2/GP73. Upregulation of GOLPH2 mRNA has been recently reported in expression array analyses of prostate cancer. As GOLPH2 protein expression in prostate tissues is currently unknown, this study aimed at a comprehensive analysis of GOLPH2 protein in benign and malignant prostate lesions. Immunohistochemically detected GOLPH2 protein expression was compared with the basal cell marker p63 and the prostate cancer marker a-methylacylCoA racemase (AMACR) in 614 radical prostatectomy specimens. GOLPH2 exhibited a perinuclear Golgi-type staining pattern and was preferentially seen in prostatic gland epithelia. Using a semiquantitative staining intensity score, GOLPH2 expression was significantly higher in prostate cancer glands compared with normal glands (Po0.001). GOLPH2 protein was upregulated in 567 of 614 tumours (92.3%) and AMACR in 583 of 614 tumours (95%) (correlation coefficient 0.113, P ¼ 0.005). Importantly, GOLPH2 immunohistochemistry exhibited a lower level of intratumoral heterogeneity (25 vs 45%). Further, GOLPH2 upregulation was detected in 26 of 31 (84%) AMACR-negative prostate cancer cases. These data clearly suggest GOLPH2 as an additional ancillary positive marker for tissue-based diagnosis of prostate cancer.

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Association Between Two Unlinked Loci at 8q24 and Prostate Cancer Risk Among European Americans

Abstract: Three loci at 8q24 are independent genetic risk factors for prostate cancer.

Cited by 122 publications

References 18 publications

Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis

Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis

Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer

GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics

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