Abstract
KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy. All subjects were from Beijing and Tianjin, including 266 cases with prostate cancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods. Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had a decreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45- 0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34, 95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P > 0.05). CONCLUSIONS. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in the United States men with over 200,000 new cases and 30,000 deaths estimated in 2010 (Jemal et al, 2010). Amundadottir et al (2006) evidenced a greater estimated Population attributable risk (PAR) (16%) that may contribute to higher incidence of prostate cancer (PCa) in African American men than in men of European ancestry (Amundadottir et al, 2006)
We evaluated associations between clinical covariates and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods
Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men
Summary
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in the United States men with over 200,000 new cases and 30,000 deaths estimated in 2010 (Jemal et al, 2010). Amundadottir et al (2006) evidenced a greater estimated Population attributable risk (PAR) (16%) that may contribute to higher incidence of PCa in African American men than in men of European ancestry (Amundadottir et al, 2006). Recent genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with PCa risk (Duggan et al, 2007; Gudmundsson et al, 2007; Yeager et al, 2007; Gudmundsson et al, 2008; Thomas et al, 2008; Gudmundsson et al, 2009; Yeager et al, 2009; Schumacher et al, 2011). Confirmation of these risk loci among European descent has been reported extensively. Conclusions. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men
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