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

Abstract

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