Long-range enhancers on 8q24 regulate c-Myc

Sotelo, Julio; Esposito, Dominic; Duhagon, Marı́a Ana; Banfield, Kelley L.; Mehalko, Jennifer; Liao, Hongling; Stephens, Robert M.; Harris, T. J. R.; Munroe, David J.; Wu, Xiaolin

doi:10.1073/pnas.0906067107

Cited by 211 publications

(193 citation statements)

References 31 publications

(49 reference statements)

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“…To date, GWASs have revealed 16 loci on chromosomal band 8q24 associated with PCa risk in various populations worldwide (Amundadottir et al, 2006;Yeager et al, 2007;Christopher et al, 2007;Schumacher et al, 2007;Robbins, 2007;Gudmundsson, 2007;Terada, 2008;Gilles Thomas et al, 2008;Salinas, 2008;Tan, 2008;, Eeles et al, 2009Gudmundsson, 2009;Liu, 2009;M et al, 2009;Takata, 2010;Liu, 2010;Liu et al, 2011;Murphy, 2012). Enhancer elements located in the 8q24 regions associated with susceptibility to PCa have been reported to increase Myc promoter activity (Sotelo et al, 2010). Among these genetic variations, the 8q24 rs4242382-A polymorphism (Ahn et al, 2011) was significantly associated with PCa risk in North American and European populations, though data for Asian populations are still rare.…”

Section: Introductionmentioning

confidence: 99%

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao

Liu²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologicallyconfirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, P=7.3×10 -5 ), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, Padj=1.1×10 -4 ). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ≥65 years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype (P=4.6×10 -5 -3.0×10 -2 ). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, P=1.0×10 -5 ) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

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Section: Introductionmentioning

confidence: 99%

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao

Liu²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The region has been extensively studied and is relatively gene-poor. A number of functional enhancers have been identified in the region 70,71 and some of these enhancers have been shown to regulate MYC.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

et al. 2012

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Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (DLOD ¼ 3.193, empirical P ¼ 0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD ¼ 2.541, DLOD ¼ 1.651, P ¼ 0.03) and 22q11.1-q11.21 (OSA LOD ¼ 2.395, DLOD ¼ 2.36, P ¼ 0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families.

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“…Multiple SNPs in this region are associated, with association being different in different populations and multiple variants in this region are associated with other cancers. 19,20,[25][26][27] Despite some effort to directly link these variants to MYC gene expression levels, no clear correlation could be found, but this region is known to interact at the chromatin level with the MYC locus. 26,27 One of the strongest SNP associations is to the rs10993994 SNP on chromosome 10, in front of the MSMB gene.…”

Section: Genome-wide Association Studies (Gwas)mentioning

confidence: 99%

“…19,20,[25][26][27] Despite some effort to directly link these variants to MYC gene expression levels, no clear correlation could be found, but this region is known to interact at the chromatin level with the MYC locus. 26,27 One of the strongest SNP associations is to the rs10993994 SNP on chromosome 10, in front of the MSMB gene. 21,23,28,29 MSMB encodes beta-microseminoprotein, an immunoglobulin binding factor family protein produced by the epithelial cells of the prostate gland and secreted into the seminal plasma.…”

Section: Genome-wide Association Studies (Gwas)mentioning

confidence: 99%

Genetics and genomics of prostate cancer

Dean¹,

Li²

2013

Asian J Androl

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Prostate cancer (PCa) is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year. Nearly all mortalities from PCa are due to metastatic disease, typically through tumors that evolve to be hormone-refractory or castrate-resistant. Despite intensive epidemiological study, there are few known environmental risk factors, and age and family history are the major determinants. However, there is extreme heterogeneity in PCa incidence worldwide, suggesting that major determining factors have not been described. Genome-wide association studies have been performed and a considerable number of significant, but low-risk loci have been identified. In addition, several groups have analyzed PCa by determination of genomic copy number, fusion gene generation and targeted resequencing of candidate genes, as well as exome and whole genome sequencing. These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53 and other potential driver genes, and the disturbance of androgen response and cell cycle pathways. It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding, diagnosing and better treating PCa.

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Long-range enhancers on 8q24 regulate c-Myc

Cited by 211 publications

References 31 publications

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

Genetics and genomics of prostate cancer

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