Xiao Li

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.

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.

Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis

Background Previous studies have investigated the relationship between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and prostate cancer susceptibility, but the results have remained controversial. This meta-analysis was therefore performed to clarify this association. Methods The databases PubMed, Embase and Web of Science were searched for relevant available studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Publication bias was estimated using Beggs funnel plots and Eggers regression test. Trial sequential analysis was used to reduce the risk of type I error and estimate whether the evidence of the results was sufficient. Results Overall, a significant increased risk of prostate cancer was associated with MnSOD Val16Ala polymorphism for the heterozygote model (OR = 1.14; 95% CI, 1.05-1.24), homozygote model (OR = 1.18; 95% CI, 1.02-1.36), dominant model (OR = 1.24; 95% CI, 1.07-1.44) and recessive model (OR = 1.10; 95% CI, 0.96-1.24). In the subgroup analysis by genotyping method, the results were statistically significant for the TaqMan and PCR-RFLP methods. In addition, when stratified by sample size, statistically significant increased risks were found among both large samples and small samples. Furthermore, when stratified by source of control, significant results were detected in both population-based controls and hospital-based controls. By trial sequential analyses, these findings in the current study were shown to be based on sufficient evidence. Conclusions This meta-analysis indicated that the Ala allele of the MnSOD gene polymorphism increases prostate cancer susceptibility.

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 GSTA1, GSTM1, GSTP1, and GSTT1 genetic polymorphisms and bladder cancer susceptibility: A meta-analysis.

Background: Previous studies have investigated the relationship between GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and bladder cancer (BCa) susceptibility, respectively, but the results remain inconsistent. So, we conducted this meta-analysis including 79 case–control studies to explore such relationships. Methods: We searched PubMed, EMBASE, Cochrane library, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were implemented to evaluate the intensity of associations. Publication bias was estimated using Begg funnel plots and Egger regression test. To assess the stability of the results, we used sensitivity analysis with the method of calculating the results again by omitting 1 single study each time. Between-study heterogeneity was tested using the I 2 statistic. Results: No significant association between GSTA1 polymorphism and BCa susceptibility (ORu200a=u200a1.05, 95% CI 0.83–1.33) was noted. Besides, meaningful association between individuals who carried the GSTM1 null genotype and increased BCa risk was detected (ORu200a=u200a1.39, 95%CI 1.28–1.51). When stratified by ethnicity, significant difference was found in both Caucasian (ORu200a=u200a1.39, 95% CI 1.23–1.58) and Asian populations (ORu200a=u200a1.45, 95% CI 1.31–1.61). Moreover, in the subgroup analysis by source of controls (SOC), the results were significant in both hospital-based control groups (ORu200a=u200a1.49, 95% CI 1.35–1.64) and population-based control groups (ORu200a=u200a1.21, 95% CIu200a=u200a1.07–1.37). Additionally, the analysis revealed no significant association between GSTP1 polymorphism and BCa risk (ORu200a=u200a1.07, 95% CI 0.96–1.20). What is more, significant associations between GSTT1 polymorphism and BCa susceptibility were discovered (ORu200a=u200a1.11, 95% CI 1.00–1.22). In the subgroup analysis by ethnicity, significant associations between GSTT1 null genotype and BCa risk were observed only in Caucasians (ORu200a=u200a1.25, 95% CI 1.09–1.44). Furthermore, when stratified by SOC, no obvious relationship was found between the GSTT1 null genotype polymorphism with hospital-based population (ORu200a=u200a1.11, 95% CI 0.97–1.28) or population-based population (ORu200a=u200a1.10, 95% CI 0.96–1.27). Conclusion: This study suggested that GSTM1 null genotype and GSTT1 null genotype might be related to higher BCa risk, respectively. However, no associations were observed between GSTA1 or GSTP1 polymorphisms and BCa susceptibility.

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

OBJECTIVEnA 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.nnnMETHODSnTaqMan 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnIn 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.

Long non-coding RNA NAP1L6 promotes tumor progression and predicts poor prognosis in prostate cancer by targeting Inhibin-β A

Background/purpose Long non-coding RNAs (lncRNAs) have emerged as key molecules in initiation and progression of prostate cancer (PCa). In this study, we aimed to explore the role of lncRNA NAP1L6 in the development and progression of PCa. Materials and methods We identified that lncRNA NAP1L6 was over-expressed both in PCa tissues and cell lines by gene expression array profiling. The expression level of NAP1L6 in 75 PCa tissues and adjacent tissues was detected by RT-PCR. Next, the correlations between NAP1L6 expression and clinical features of patients with PCa were analyzed by paired t-test or chi-squared test, and its association with patient prognosis was assessed by the Kaplan–Meier method. The effects of NAP1L6 on PC-3 and 22RV1 cells were evaluated by Cell Counting Kit-8 (CCK-8), migration, invasion, and colony formation assays. Further analysis of the results of the microarray was performed to find downstream gene of NAP1L6. Cell function experiments were performed in order to explore the relationship between NAP1L6 and Inhibin-β A (INHBA) and the specific mechanism by which INHBA affects the development of PCa. Results Using microarray analysis, we identified 412 lncRNAs and 1245 mRNAs to be significantly differentially expressed in three PCa samples when compared with adjacent non-tumor tissues (ANTT) (fold-change ≥2.0 or ≤0.5, P<0.05, false discovery rate (FDR) <0.05). NAP1L6 expression was upregulated in PCa tissues and cell lines (both P<0.05) compared with ANTT. Besides, high expression level of NAP1L6 promotes PCa cell proliferation, migration, and invasion (all P<0.05), and is significantly associated with larger tumor diameter, distant metastasis, and shorter survival time (all P<0.05). We found that NAP1L6 promoted the expression of INHBA (P<0.05), and knockdown of NAP1L6 led to the reduction of PCa cell migration, invasion, and proliferation by regulating the expression of INHBA (all P<0.05). Conclusion lncRNA NR6A1 might play an oncogenic role in PCa initiation and progression by regulating the expression of INHBA, and might act as a novel prognostic biomarker for PCa treatment.

Genetic variants in macrophage colony-stimulating factor are associated with risk of renal cell carcinoma in a Chinese population

Objective: This study was performed to investigate whether CSF-1 polymorphisms influenced the risk of renal cell carcinoma in a Chinese population. Methods: The potentially functional polymorphisms in CSF-1 (rs333951 and rs2050462) were genotyped in this hospital-based case-control study, comprising 1512 renal cell carcinoma patients and 1691 controls in a Chinese population using the TaqMan assay. Furthermore, odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate such an association. The logistic regression was used to assess the association between these genetic polymorphisms and the risk of renal cell carcinoma. Results: We found the genotype and allele frequency distribution of rs2050462 were significantly associated with the increasing risk of renal cell carcinoma (P = 0.007). However, no statistical significance was found in the association between CSF-1 rs333951 polymorphism and the susceptibility of renal cell carcinoma (P = 0.589). The analysis of combined risk alleles revealed that patients with two to four risk alleles showed no elevated risk of renal cell carcinoma compared to those with zero to one risk alleles (adjusted OR 1.09; 95% CI 0.95, 1.26; P = 0.226). Furthermore, compared with the genotypes containing A allele (AC and AA), the patients carrying the CC genotype in rs2050462 had a significantly greater prevalence of clinical stage II and IV (adjusted OR 0.67; 95% CI 0.47, 0.94; P = 0.021; adjusted OR 0.50; 95% CI 0.29, 0.88; P = 0.015, respectively). Conclusions: The functional rs2050462 in CSF-1 might have a substantial influence on the renal cell carcinoma susceptibility and evolution in the Chinese population.

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. n 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. n 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.