Abstract
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. Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically- confirmed 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. 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. 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.
Highlights
The prevalence of prostate cancer (PCa) and the frequencies of risk alleles differ across populations, and it is important for understanding the effects of these genetic polymorphisms in people of different ethnic backgrounds
A meta-analysis of the association between PCa risk and genotype was performed on data from 1793 PCa cases and 1864 controls derived from the current study population and from populations in previously published studies in American and European populations
The prevalence of PCa and the allele frequencies differ among populations and area, and it is important to understand the effects of ethnicity and region on these markers
Summary
The prevalence of prostate cancer (PCa) and the frequencies of risk alleles differ across populations, and it is important for understanding the effects of these genetic polymorphisms in people of different ethnic backgrounds. 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; 2008, Eeles et al, 2009; Al Olama, 2009; Gudmundsson, 2009; Liu, 2009; M et al, 2009; 2010; 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. We investigated the association between the rs4242382-A variant at 8q24 and PCa in Chinese men, and compared our data with previous results from other populations by meta-analysis, to clarify the significance of the locus in multi-ethnic populations
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