Mkk4 Gene Polymorphism (1304 T > G) And The Functional Change Of The Study Of The Relationship Between Prostate Cancer Susceptibility

Purpose MKK4has been suggested as a tumor suppressor. The functional variant(-1304T>G) in the MKK4promoter has been implicated as a risk factor for manytypes of cancer. However, its role in prostate cancer (PCa) is unclear. To determinewhether this SNP constitutes a risk factor for PCa susceptibility and to derive a moreprecise estimation of the associations between this SNP and cancers risk, weperformed a case-control study and then a meta-analysis covering previouscase-control studies.Methods In this study,222male patients with PCa and244cancer-free controlswere evaluated MKK4-1304T>G genotype. The transcriptional activity of MKK4gene was measured by luciferase assay and MKK4serum expression was measuredby ELISA.Results As a whole, we found that compared to the most common-1304TTgenotype, carriers of-1304G variant genotypes had a decreased risk of PCa (OR=0.670;95%CI=0.452–0.993, P=0.046for TG, and OR=0.647;95%CI=0.441–0.948, P=0.025for TG+GG). We found that carriers of the-1304G variantgenotypes had greater transcriptional activity and serum expression of MKK4thancarriers of the-1304T allele. Our meta-analysis also suggested that the-1304G variant contributes to decreased risk of various cancers.Conclusion Our results suggest that the functional-1304G variant in the MKK4promoter 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 ourfindings.