Multiple Independent Genetic Variants in the 8q24 Region Are Associated with Prostate Cancer Risk

Salinas, Claudia A.; Kwon, Erika M.; Carlson, Christopher S.; Koopmeiners, Joseph S.; Feng, Ziding; Karyadi, Danielle M.; Ostrander, Elaine A.; Stanford, Janet L.

doi:10.1158/1055-9965.epi-07-2811

Cited by 68 publications

(74 citation statements)

References 31 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%

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%

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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“…Single nucleotide polymorphisms (SNPs) in several genetic loci like 8q24, 22q13 and 17q12 were reported to be linked to PCa susceptibility, early onset of the disease and tumor agressiveness (Al Olama, et al, 2014; Berndt, et al, 2015; Chang, et al, 2009; Cheng, et al, 2009; Eeles, et al, 2009; Eeles, et al, 2013; Gudmundsson, et al, 2009; Helfand, et al, 2015; Levin, et al, 2008; Salinas, et al, 2008; Schumacher, et al, 2011; Takata, et al, 2010; Thomas, et al, 2008; Witte, 2007). Although little is known about the functional aspect of risk SNPs, some studies showed cancer SNPs predominately present in multiple putative regulatory elements (2011; Sille, et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

Narisu

Schlick

et al. 2015

Human Mutation

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Genome-wide association studies have identified genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-IP coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH), was within a novel putative auxiliary AR binding motif, which is enriched in the neighborhood of canonical androgen responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of melanophilin in primary prostate tumors was significantly lower in those with the G compared to the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favourable PCa risk profile points out a tumor suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH.

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“…(Gudmundsson, 2007;Murphy, 2012) Asian studies, however, have been restricted to one Japanese GWAS, one Chinese replication study (Liu et al, 2011) and several small-scale studies in Japanese, Taiwanese and southern Chinese populations (Terada, 2008;M et al, 2009;Liu, 2009;M et al, 2010;Takata, 2010;Liu, 2010). 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).…”

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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Multiple Independent Genetic Variants in the 8q24 Region Are Associated with Prostate Cancer Risk

Cited by 68 publications

References 31 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

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

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

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