Manganese superoxide dismutase polymorphism and prostate cancer risk:a meta-analysis

Objective： MnSOD plays a vital role in carcinogenesis, partly in that it converts superoxide radical to oxygen and hydrogen peroxide. The conflicting results of studies on the role of MnSOD polymorphism （Val-9Ala） with the risk of prostate cancer encouraged us to perform a meta-analysis to examine the association. Methods： A comprehensive search was conducted to examine all the eligible studies of MnSOD polymorphism and prostate cancer risk. We used odds ratios （ORs） with 95% confidence intervals （CIs） to assess the strength of the association. The pooled estimates of ORs were computed using the fixed-effects model or randomeffects model. Results： Ten eligible studies, including 4 608 cases and 5 861 controls, were included in this meta-analysis. Overall, individuals with Ala/Ala and Ala/Val genotypes have an increased risk of prostate cancer, compared with those carrying the Val/Val genotype （Ala/Ala vs. Val/Val： OR=1.13; 95% CI=1.02～1.25; P = 0.020, Pheterogescily=0.370; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.25; P = 0.004, Phctrogrnety=0.940）. This significant association was also found in a dominant model with -9Ala allele （Ala/ Ala＋Ala/Val vs. Val/Val： OR=1.12; 95% CI： 1.03～1.22; P = 0.009, Pheterogeneity=0.64）. In the subgroup by ethnicity, it Was observed that significantly elevated prostate cancer risk was associated with -9Ala allele in Caucasians （Ala/Ala vs. Val/Val： OR=l.14; 95% CI=1.03～1.27; P = 0.01, Pheterogeselity=0.31; Ala/Val vs. Val/Val： OR=1.14; 95% CI=1.04～1.24; P = 0.006, Pheterogeneity=0.87） but not in African-Americans. Furthermore, this meta-analysis showed that the -9Ala allele was associated with both nonaggressive and aggressive prostate cancer risks. Conclusion： Our meta-analysis suggests that MnSOD Val-9Ala polymorphism is associated with prostate cancer risk, especially in Caucasians.

The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma

The purpose of this study was to determine the relationship between hypermethylation of DACT1 gene pro-moter and lower mRNA expression in bladder urothelial carcinoma tissue.The methylation status of 29 urothelial carcinoma samples and 29 normal tissue samples were examined by methylation-specific polymerase chain reac-tion（MSP）.The DACT1 mRNA transcript levels and DACT1 protein levels in all samples were then evaluated to define the relationship between the methylation status of the DACT1 promoter and its expression at the transcrip-tional and translational levels.Decreased expression of DACT1 was detected in 89.66% of urothelial carcinomas（26/29;P 〈 0.005）.Promoter hypermethylation was found in 58.62%（17/29） urothelial carcinomas and 25%（7/29） normal tissues,respectively（P 〈 0.05）.DACT1 expression was lower in tissues where the DACT1 gene promoter was hypermethylated than in unmethylated tissues（0.25±0.17 vs 0.69±0.30,P 〈 0.05）.DACT1 gene hyper-methylation was closely related to tumor size,grade and stage（P 〈 0.05）.Our results indicate that silencing and downregulation of DACT1 mRNA may be implicated in carcinogenesis and the progression of bladder urothelial carcinoma,and may be a potential prognostic factor.

MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder

The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 （IGF-2） gene and methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism （RFLP）, PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis （46.3% vs 17.2%, P = 0.018）. No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 （95% CI=1.06-10.59） for CT and 4,95 （95% CI=1.18-12.74） for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.

Construction and identification of recombinant lentiviral vector containing HIV-1 Tat gene and its expression in 293T cells

Objective： To construct a lentiviral vector expressing HIV-1 Tat and identify its expression in 293T cells. Methods： The gene fragment of HIV-1 Tatlol was subcloned to lentiviral transfer vector pHAGE-CMV-MCS- IZsGreen, which was named pHAGE-Tat. Then the constructed pHAGE-Tat was used to co-transfect the packing 293T cells, together with the packaging plasmids pMD2.G and psPAX2. The packaged viral particles designated LV-Tat were used to infect the 293T cells and the viral titer was calculated. The expression of HIV-1 Tat in 293T cells was confirmed using RT-PCR and western blot. Results： The recombinant lentiviral vector was successfully constructed and could express HIV-1 Tat in 293T cells. The virus titer was 5.73×10^6 ifu/ml. Conclusion： The successfully constructed recombinant lentiviral vector makes a strong foundation for further exploring the possible role of HIV-1 Tat in the development of prostate cancer.

CYP17 T27C polymorphism and prostate cancer risk: a meta-analysis based on 31 studies

Objective：The cytochrome P450 17α-hydroxylase（CYP17）plays a vital role in androgen biosynthesis.A T-to-C polymorphism in the 5＇promoter region of CYP17 has been implicated as a risk factor for prostate cancer,but the results of individual studies are inconclusive or controversial.To derive a more precise estimation of the relationship,we performed an updated meta-analysis from 31 studies based on 27 publications.Methods：A comprehensive search was conducted to examine all the eligible studies of CYP17 polymorphism and prostate cancer risk.We used odds ratios（ORs）with 95%confidence intervals（CIs）to assess the strength of the association.Results：Overall,individuals with CC/CT genotype were not associated with prostate cancer risk （CC vs.TT：OR=1.03,95%CI=0.86-1.24,P=0.72,P heterogeneity 〈0.0001;CT vs.TT：OR=0.99,95%CI=0.87- 1.12,P=0.88,P heterogeneity =0.0006）.In the stratified analysis by ethnicity,there was a significantly increased risk of prostate cancer among individuals of African descent under the recessive model（OR=1.56,95%CI=1.01- 2.39,P=0.04,P heterogeneity =0.65）.Conclusion：This meta-analysis suggested that CYP17 polymorphism might be associated with prostate cancer risk among individuals of African descent.