Role of the functional MKK4 promoter variant (-1304T>G) in a decreased risk of prostate cancer: case-control study and meta-analysis

MKK4 has been suggested as a tumor suppressor. The functional variant (-1304T > G) in the MKK4 promoter has been implicated as a risk factor for many types of cancer. However, its role in prostate cancer (PCa) is unclear. To determine whether this SNP constitutes a risk factor for PCa susceptibility and to derive a more precise estimation of the associations between this SNP and cancer risk, we performed a case-control study and then a meta-analysis covering previous case-control studies. In this study, 222 male patients with PCa and 244 cancer-free controls were evaluated MKK4-1304T > G genotype. The transcriptional activity of MKK4 gene was measured by luciferase assay, and MKK4 serum expression was measured by ELISA. As a whole, we found that compared to the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of PCa (OR = 0.670; 95 % CI = 0.452-0.993, P = 0.046 for TG, and OR = 0.647; 95 % CI = 0.441-0.948, P = 0.025 for TG + GG). We found that carriers of the -1304G variant genotypes had greater transcriptional activity and serum expression of MKK4 than carriers of the -1304T allele. Our meta-analysis also suggested that the -1304G variant contributes to decreased risk of various cancers. Our results suggest that the functional -1304G variant in the MKK4 promoter decreases the risk of PCa by increasing the promoter activity. In the future, prospective researches on patients from many parts of the world may validate our findings.