Zicheng Xu

P53 Arg72Pro Polymorphism and Bladder Cancer Risk - Meta- analysis Evidence for a Link in Asians but not Caucasians

OBJECTIVE Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship, we performed this systemic review and meta-analysis based on 15 publications. METHODS We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. RESULTS We found that there was no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/ Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg (OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32). However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison (Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Pro plus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of an association between bladder cancer risk and P53 genotype was observed among Caucasian population in any genetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.56 95%CI 0.26-1.20; Recessive model, OR=0.62 95%CI 0.35-1.08) between P53 codon 72 polymorphism and bladder cancer in all comparisons. CONCLUSIONS Despite the limitations, the results of the present meta-analysis suggest that, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancer in Asians; and there are no association between genotype distribution and the stage of bladder cancer.

Effectiveness of Prophylactic Surgeries in BRCA1 or BRCA2 Mutation Carriers: A Meta-analysis and Systematic Review

Purpose: To systematically investigate the effectiveness of prophylactic surgeries (PS) implemented in women carrying BRCA1/2 mutations. Experimental Design: The PubMed database was searched till August 2014 and 15 studies met the inclusion criteria. Fixed- or random-effects models were conducted according to study heterogeneity. We calculated the pooled relative risks (RR) for cancer risk or mortality along with 95% confidence intervals (CI). Results: Prophylactic bilateral salpingo-oophorectomy (PBSO) and bilateral prophylactic mastectomy (BPM) were both associated with a decreased breast cancer risk in BRCA1/2 mutation carriers (RR, 0.552; 95% CI, 0.448–0.682; RR, 0.114; 95% CI, 0.041–0.317, respectively). Similar findings were observed in BRCA1 and BRCA2 mutation carriers separately. Moreover, contralateral prophylactic mastectomy (CPM) significantly decreased contralateral breast cancer incidence in BRCA1/2 mutation carriers (RR, 0.072; 95% CI, 0.035–0.148). Of note, PBSO was associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers without breast cancer (HR, 0.349; 95% CI, 0.190–0.639) and those with breast cancer (HR, 0.432; 95% CI, 0.318–0.588). In addition, all-cause mortality was significantly lower for patients with CPM than those without (HR, 0.512; 95% CI, 0.368–0.714). However, BPM was not significantly associated with reduced all-cause mortality. Data were insufficient to obtain separate estimates of survival benefit with PS in BRCA1 or BRCA2 mutation carriers. Conclusions: BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971–81. ©2016 AACR.

Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: a meta-analysis of 11 cohort studies

Diabetes mellitus is associated with a decreased risk of prostate cancer. However, previous studies examining the associations between diabetes mellitus and prostate cancer prognosis have produced mixed results. Here, we aim to summarize the effect of diabetes mellitus on prostate cancer prognosis.

Comparison between transrectal and transperineal prostate biopsy for detection of prostate cancer: a meta-analysis and trial sequential analysis

To systematically assess the efficacy and complications of transrectal (TR) versus transperineal (TP) prostate biopsy in the detection of prostate cancer (PCa). A meta-analysis was performed by searching the databases Pubmed, Embase and Web of science for the relevant available studies until September 1st, 2016, and thirteen studies met the inclusion criteria. The pooled odds ratios with 95% confidence intervals were calculated to evaluate the differences of TR and TP groups in PCa detection rate. Then, trial sequential analysis was performed to reduce the risk of type I error and estimated whether the evidence of the results was reliable. Overall, this meta-analysis included a total of 4280 patients, who had been accrued between April 2000 and Aug 2014 and randomly divided into TR group and TP group. Prostate biopsies included sextant, extensive and saturation biopsy procedures. Patients who received TP prostate biopsy had no significant improvement in PCa detection rate, comparing TR group. Moreover, when comparing TR and TP studies, no significant difference was found in abnormal DRE findings, serum PSA level measurement, Gleason score, prostate volume. Besides, this meta-analysis showed no obvious differences between these two groups in terms of relevant complications. Therefore, this meta-analysis revealed that no significant differences were found in PCa detection rate between TP and TR approaches for prostate biopsy. However, with regard to pain relief and additional anesthesia, TR prostate needle biopsy was relatively preferable, compared to TP prostate biopsy.

Chemotherapy with or without estramustine for treatment of castration-resistant prostate cancer: A systematic review and meta-analysis.

Background:Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in order to assess the efficacy and toxicity of combining estramustine with chemotherapy for the treatment of CRPC. Methods:Relevant randomized clinical trials were systematically searched from the databases Pubmed, Embase, and Web of science up to April 1, 2016. Data were centrally extracted and analyzed from the previous studies by 2 independent reviewers. The primary endpoint was overall survival (OS) with pooled hazard ratios. Secondary endpoints were prostate-specific antigen (PSA) response and grade 3 or 4 toxicity using pooled odds ratios. Stata version 12.0 software was used for statistical analysis. Results:Overall, this meta-analysis identified 9 eligible articles, including a total of 956 patients, who had been accrued between January 1, 1993 and December 1, 2010 and randomly divided into chemotherapy with estramustine and without estramustine. Chemotherapy (with or without estramustine) consisted of docetaxel, paclitaxel, ixabepilone, epirubicin, and vinblastine. Patients who received chemotherapy with estramustine had a better improvement in PSA response rate, comparing those without estramustine (OR = 1.84, 95% CI = 1.20–2.80). However, OS between the 2 groups indicated no significant differences (HR = 0.90, 95% CI = 0.77–1.05). Besides, these results of meta-analysis showed no obvious differences between these 2 groups in grade 3 or 4 adverse effects, including anemia (OR = 0.78, 95% CI = 0.38–1.57), neutropenia (OR = 0.91, 95% CI = 0.59–1.43), thrombocytopenia (OR = 0.68, 95% CI = 0.19–2.42), nausea (OR = 2.34, 95% CI = 0.81–6.72), vomiting (OR = 2.43, 95% CI = 0.69–8.51), diarrhea (OR = 3.45, 95% CI = 0.93–12.76), fatigue (OR = 0.67, 95% CI = 0.32–1.41), neuropathy (OR = 0.54, 95% CI = 0.21–1.44), allergic reaction (OR = 1.60, 95% CI = 0.37–6.84), thromboembolic event (OR = 2.18, 95% CI = 0.86–5.51), and edema (OR = 1.02, 95% CI = 0.18–5.95). Conclusions:This meta-analysis indicated chemotherapy with additional estramustine increased the PSA response rate. However, OS and grade 3 or 4 toxicity were not improved for these patients with CRPC.

Expressions of stem cell transcription factors Nanog and Oct4 in renal cell carcinoma tissues and clinical significance

Abstract We aimed to detect the expressions of stem cell transcription factors Nanog and Oct4 in renal cell carcinoma (RCC) tissues. Nanog and Oct4 mRNA expressions in RCC tissues significantly exceeded those in paracancerous tissues (p < 0.01 and p < 0.05), being positively correlated with histological grade (p < 0.01 and p < 0.05) and TNM stage (p < 0.05). With increasing TNM stage (p < 0.01) and lymphatic metastasis (p < 0.05), the positive expression rate of Nanog protein increased. RCC patients with low Nanog and Oct4 expressions in tumor tissues had significantly higher survival rates (p < 0.05). High Nanog and Oct4 expressions may be potential therapeutic targets.

Association of N-acetyltransferase 1 polymorphism and bladder cancer risk: an updated meta-analysis and trial sequential analysis

Background Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. Methods A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. Results There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. Conclusions Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1* 10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.

The relationship between functional promoter -94 ins/del ATTG polymorphism in {NF-κ B1} gene and the risk of urinary cancer

OBJECTIVE A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NF-κ B1 gene was reported to influence NF-κ B1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with the risk of urinary cancer, including renal cancer, bladder cancer and prostate cancer. METHODS TaqMan method was applied to genotype the NF-κ B1 -94 ins/del ATTG promoter polymorphism in three case-control studies: renal cell carcinoma group (1216 cases and 1588 controls), bladder cancer group (730 cases and 780 controls), and prostate cancer group (820 cases and 945 controls). Logistic regression was used to assess the association between the polymorphism and urinary cancer risk. RESULTS The del/del genotype was detected to be associated with a statistically significant increased risk of bladder cancer when taking the ins/ins genotypes as reference (P < 0.001, adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52). Furthermore, in bladder cancer, the same results were observed in the del/del genotype compared with the ins/ins + ins/del genotypes (P < 0.001, OR = 1.82, 95% CI = 1.41-2.35), and the del allele compared with the ins allele (P < 0.001, OR = 1.29, 95% CI = 1.12-1.49). However, no significant difference was observed in the associations between the NF-κ B1 polymorphism and the risk of renal cell carcinoma or prostate cancer in all kinds of models. CONCLUSIONS In the Chinese population, the -94 ins/del ATTG polymorphism in NF-κ B1 promoter may contribute to the etiology of bladder cancer instead of renal cell carcinoma or prostate cancer.

Docetaxel Combined With Cisplatin for Metastatic Extramammary Paget Disease

Micro‐Abstract We provided docetaxel combined with cisplatin to patients with metastatic extramammary Paget disease (EMPD). After 2 cycles of chemotherapy, 4 patients experienced partial remission and 4 stable disease; mean overall survival (OS) was 28.9 months, and mean progression‐free survival was 9.9 months. Docetaxel combined with cisplatin might be a treatment option for metastatic EMPD, with good disease control rate and OS. Introduction: Metastatic extramammary Paget disease (EMPD) as a rare intraepithelial carcinoma is fatal. However, no standardized chemotherapy has been established. We provided docetaxel combined with cisplatin to EMPD patients. Patients and Methods: A total of 8 patients with metastatic EMPD were included in this study between July 2010 and July 2015 (mean age, 64.4 years); they underwent a mean of 9.4 cycles of chemotherapy. All the patients were treated with chemotherapy (docetaxel 60 mg/m2 on day 1; cisplatin 25 mg/m2 on days 1‐3) as first‐line treatment for > 6 cycle (at least 21 days per cycle). Data on tumor response, time to progression, overall survival, and adverse events were collected. Results: After 2 cycles of chemotherapy, 4 patients experienced partial remission and 4 stable disease. The mean overall survival was 28.9 months, and the mean progression‐free survival was 9.9 months. Conclusion: Docetaxel combined with cisplatin might be a treatment option for metastatic EMPD, with high disease control rate and good overall survival.

The association between let-7 microRNA-binding site polymorphism rs712 and cancer risk: a meta-analysis and trial sequential analysis

Background: Previous studies have investigated the relationship between let-7 microRNA-binding site polymorphism rs712 and cancer susceptibility. However, the available conclusions remained inconsistent. The present meta-analysis was thus performed to clarify such associations. Methods: A meta-analysis including 11 studies was performed with 3,572 cases and 4,749 controls. Relevant studies were searched in the databases EMBASE, PubMed and Web of Science, covering relevant papers published until September 1st, 2016. We pooled data with odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Besides, Begg’s funnel plots and Egger’s regression test were utilized to evaluate publication bias. Furthermore, we took advantage of trial sequential analysis to evaluate whether the evidence of the results was sufficient. Results: Overall, the results showed that significant cancer risk was associated with rs712 for heterozygote model OR =1.10 (95% CI: 1.002–1.22), homozygote model OR =1.71 (95% CI: 1.18–2.49), dominant model OR =1.19 (95% CI: 1.04–1.35), recessive model OR=1.64 (95% CI: 1.17–2.31) and allele model OR =1.21 (95% CI: 1.06–1.39). Moreover, trial sequential analyses for the first time were performed to confirm such associations, demonstrating that the results of our study were based on sufficient evidence. Conclusions: This results of the meta-analysis suggested that rs712 polymorphism was associated with cancer susceptibility, which might act as a potential biomarker for evaluating cancer risk.