Association of FOXP4 Gene with Prostate Cancer and the Cumulative Effects of rs4714476 and 8q24 in Chinese Men.

Background: The tumor suppressor forkhead box P4 (FOXP4) plays important roles in oncogenesis, and the FOXP4 variant rs1983891 is associated with prostate cancer (PCa) in several studies. However, association studies conducted in Northern and Southern Chinese have provided conflicting results. Therefore, here we performed fine mapping of FOXP4 to identify the association with PCa and the potential application in Chinese men. Methods: We examined 11 variants spaced approximately 55 kb apart spanning FOXP4 using high-resolution melting-curve analysis and sequencing methods in 286 PCa patients and 630 controls, and the association between these variants and PCa risk was evaluated. Additionally, we evaluated the cumulative effect of rs4714476 and 2 variants in 8q24 (rs16901966, rs10090154) confirmed in our previous study. Results: Of 11 SNPs, only rs4714476-C at the 5' near gene of FOXP4 was associated with increased age-adjusted PCa risk (p = 0.012, OR = 1.32, 95% CI = 1.06 - 1.63) and aggressive PCa (p = 0.026). The CG haplotype covering rs4714476-C demonstrated significant differences between PCa cases and controls (p = 0.009). The cumulative effect analysis showed men who carried any combination of 1, 2, or 3 risk genotypes had a gradually increased PCa risk (age-adjusted OR is from 1.244 to 3.312). Conclusions: These data suggest that rs4714476 at the 5' near gene of FOXP4 potentially contributes to the susceptibility of PCa in Chinese men. The cumulative effect of rs4714476 at FOXP4 and 8q24 could increase PCa risk.