title: Role of the functional MKK4 promoter variant (-1304T>G) in a decreased risk of prostate cancer: case-control study and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shao
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Jiang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Ning-Han
authors.initials: NH
authors.lastname: Feng
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Hua
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D008156:Luciferases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human