Taijie Li

Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis

BackgroundIt has been postulated that non-steroidal anti-inflammatory drugs (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years, NSAIDs’ role in PCa development has been extensively studied; however, there is not yet a definitive answer. Moreover, the epidemiological results for NSAIDs’ effect on PCa-specific mortality have been inconsistent. Therefore, we performed a meta-analysis to examine the controversy.MethodsWe performed a literature database search and included all published studies conducted in the general population exposed to any NSAID, extracting an odds ratio (OR) or a hazard ratio (HR) with 95% confidence intervals (95% CIs) that compared the incidence of PCa or PCa-specific mortality with non-exposure. We derived a pooled OR or HR using random or fixed effects models, as appropriate. Subgroup analyses were also performed.ResultsThirty-nine studies (20 case–control and 19 cohort studies) were included in this analysis. Thirty-one studies were available concerning NSAID use and PCa incidence and eight studies on PCa-specific mortality. Compared to non-use, aspirin use was statistically significantly associated with PCa incidence risk, and the association was slightly stronger for advanced PCa than for total PCa (OR = 0.92, 95% CI = 0.87 to 0.97 for total PCa; OR = 0.81, 95% CI = 0.73 to 0.89 for advanced PCa). Aspirin use seems also to be associated with a modest reduction in PCa-specific mortality (HR = 0.86, 95% CI = 0.78 to 0.96 for total PCa; OR = 0.81, 95% CI = 0.71 to 0.92 for advanced PCa). Generally, the pooled effects for any NSAIDs, NA-NSAIDs and cyclooxygenase-2 inhibitors demonstrated no adverse or beneficial effects on PCa development or PCa-specific mortality, but the results were not consistent. The effect estimates did not vary markedly when stratified by study design and study quality but varied by geographic region. Furthermore, long-term aspirin use (≥4 years) was also significantly associated with reduced PCa incidence (OR = 0.88, 95% CI 0.79 to 0.99).ConclusionsThe present meta-analysis provides support for the hypothesis that aspirin use is inversely related to PCa incidence and PCa-specific mortality. The effect estimates, varying by geographic region, deserve further investigation.

Effect of statin on risk of gynecologic cancers: a meta-analysis of observational studies and randomized controlled trials.

Objective. Epidemiologic and clinical findings are inconsistent concerning the risk for gynecologic cancers associated with statin use. We conducted a detailed meta-analysis of all relevant original studies to evaluate the effects of statin on the risk of gynecologic cancers. Methods. We searched PubMed, Embase, and Cochrane library databases up to February 2014 looking for eligible studies. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were used to calculate the risk using random-effects models. Results. A total of 14 (4 randomized controlled trials, 5 cohorts, and 5 case-control) studies, involving 12,904 gynecologic cancer cases, contributed to the analysis. Pooled results indicated a non-significant decrease of total gynecologic cancer risk among statin users (RR=0.89; 95% CI, 0.78-1.01). Stratified analyses across cancer site revealed a modest protective effect of statin on ovarian cancer (RR=0.79; 95% CI, 0.64-0.98), while no association was found for endometrial cancer (RR=0.90; 95% CI, 0.75-1.07). The effect of statin use against cervical cancer and vulvar cancer is not conclusive. Furthermore, long-term statin use (>5years use) did not significantly affect the risk of endometrial cancer (RR=0.69; 95% CI, 0.44-1.10), but had an obvious decrease on the risk of ovarian cancer (RR=0.48; 95% CI, 0.28-0.80). Conclusions. Our results suggest that statin use was inversely associated with ovarian cancer risk, and the association was stronger for long-term statin use (>5years). The evidence for a protective effect of statin use against other gynecologic cancers is suggestive but not conclusive, which deserves further investigation.

Association of IL27 gene polymorphisms and HBV-related hepatocellular carcinoma risk in a Chinese population

BACKGROUND AND OBJECTIVE Hepatocellular carcinoma (HCC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-27 (IL-27) is a novel IL-12 family member which plays an important role in antitumor immunity. Mutations in the IL27 gene may lead to altered cytokine production and/or activity and thus modulate individuals susceptibility to HCC. In this study, we investigated the association between IL27 gene polymorphisms and HBV-related diseases risk in a Chinese population. METHODS Studied subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related HCC, and 105 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and polymerase chain reaction-sequence specific primer (PCR-SSP) strategy were used to detect IL27 gene -964A/G and 2905T/G polymorphisms, respectively. DNA sequencing was used to validate genotype results. RESULTS There were no significant differences in the genotype and allele frequencies of IL27 gene polymorphisms between the groups of patients and healthy controls. Furthermore, no association was found between the distributions of the haplotypes and HCC risk. CONCLUSION These findings indicate that the genetic variants in IL27 gene may not contribute to HCC development. Further studies with large sample size should be conducted to validate this association.

Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis.

BackgroundCatechol-O-methyltransferase (COMT) is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC) risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study.MethodsSystematic searches of the PubMed, Embase and Cochrane Library were performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.ResultsA total of 56 studies including 34,358 breast cancer cases and 45,429 controls were included. Overall, no significant associations between the COMT Val158Met polymorphism and breast cancer risk were found for LL versus HH, HL versus HH, LL versus HL, recessive model LL versus HL+HH, and dominant model LL+HL versus HH. In subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models.ConclusionOur meta-analysis results suggest that the COMT Val158Met polymorphism may not contribute to breast cancer susceptibility.Virtual slidesThe virtual slides(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs4806123577708417

Clinicopathological and prognostic significance of S100A4 overexpression in colorectal cancer: a meta-analysis

BackgroundAccumulated evidence has indicated a correlation between S100A4 expression and colorectal cancer (CRC) progression. However, its prognostic significance for patients with CRC remains inconclusive. To clarify their relationship, a meta-analysis of the relevant published studies was performed.MethodPubMed, Cochrane Library, and Web of Science databases were electronically searched. All studies evaluating the prognostic value of S100A4 expression in CRC patients regarding survival and a series of clinicopathological parameters were included. The effect of S100A4 expression on the overall survival (OS) and disease-free survival (DFS) were measured by pooled hazard ratios (HRs) and 95% confidence intervals (CIs), while the effect of S100A4 expression on the clinicopathological parameters were measured by the pooled odds ratios (ORs) and their 95% CIs.ResultsEleven studies (2,824 patients in total) were included in the meta-analysis. Overall, S100A4 overexpression was significantly associated with worse OS (HR = 1.90, 95% CI: 1.58–2.29, P <0.001), and worse DFS (HR = 2.16, 95% CI: 1.53–3.05, P <0.001) in patients with CRC. Subgroup analyses showed that S100A4 overexpression was significantly correlated with poor OS in Asian, European, and Australian patients and patients treated with surgery or chemotherapy. Additionally, there were significant associations between S100A4 expression and several clinicopathological parameters (tumour location, lymph node metastasis, nodal status, TNM stage, and tumour depth).ConclusionsThis meta-analysis indicates that S100A4 overexpression seems to correlate with tumour progression and poor prognosis of CRC patients. It may be a useful marker to predict progression and prognosis of CRC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8643820431072915

Kidney Stones and Cardiovascular Risk: A Meta-analysis of Cohort Studies

BACKGROUND Recent epidemiologic evidence suggests an association between kidney stones and incident cardiovascular disease after adjusting for other cardiovascular risk factors, but results are inconsistent. STUDY DESIGN Meta-analysis of cohort studies. SETTING & POPULATION Patients with kidney stones. SELECTION CRITERIA FOR STUDIES Cohort studies with data for kidney stones and cardiovascular morbidity identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings through February 27, 2014. PREDICTOR Kidney stones as determined by physician diagnosis, clinical coding, or self-reported scales. OUTCOMES Cardiovascular disease, coronary heart disease (CHD), and stroke. RESULTS 6 cohort studies that contained 49,597 patients with kidney stones and 3,558,053 controls, with 133,589 cardiovascular events, were included. Pooled results suggested that kidney stones were associated with an increased adjusted risk estimate for CHD (HR, 1.19; 95% CI, 1.05-1.35; P=0.05; n=6 cohorts) and stroke (HR, 1.40; 95% CI, 1.20-1.64; P<0.001; n=3 cohorts). In particular, kidney stones conferred HRs of 1.29 (95% CI, 1.10-1.52; n=6 cohorts) and 1.31 (95% CI, 1.05-1.65; n=4 cohorts) for myocardial infarction and coronary revascularization, respectively. Moreover, the pooled female cohorts showed a statistically significant association (HR, 1.49; 95% CI, 1.21-1.82; n=4 cohorts), whereas the male cohorts showed no association (HR, 1.15; 95% CI, 0.89-1.50; n=2 cohorts). LIMITATIONS Results may be limited by substantial heterogeneity, likelihood of residual confounding, and paucity of studies that separately evaluated for effect modification by sex. CONCLUSIONS Kidney stones were associated with increased cardiovascular risk, including the risk for incident CHD or stroke. There is some suggestion that the risk may be higher in women than men. Further prospective studies are needed to determine whether the association is sex specific.

Association between Tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis

BackgroundTumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-α gene, −308G/A and −238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis.MethodsWe conducted a comprehensive literature search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature database (CBM), and the China National Knowledge Infrastructure (CNKI). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI).ResultsIn this meta-analysis, we included 14 studies with 5,757 patients and 6,137 control subjects for the TNF-α-308G/A polymorphism and 1,967 patients and 2,004 control subjects for the TNF-α-238C/T polymorphism. A significantly increased prostate cancer risk was found to be associated with the TNF-α-308C/T polymorphism in studies with healthy volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093–2.145; P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047–2.085; P = 0.026). No significant association was found between the TNF-α-238G/A polymorphism and prostate cancer risk in the overall or subgroup analyses. There was no risk of publication bias in this meta-analysis.ConclusionsOur results suggest that while the TNF-α-238G/A polymorphism may not be associated with prostate cancer the TNF-α-308C/T polymorphism may significantly contribute to prostate cancer susceptibility in healthy volunteers.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1629288120116301

Meta-analysis of the association between CR1 polymorphisms and risk of late-onset Alzheimer's disease.

CR1 polymorphisms have been reported to be associated with late-onset Alzheimers disease (LOAD) susceptibility. The findings of these studies, however, have been inconsistent. Therefore, we performed a meta-analysis to assess the association between CR1 variants and LOAD susceptibility. We retrieved all relevant studies of the associations between CR1 polymorphisms and the susceptibility to LOAD for the period up to March 30, 2014. The strength of the association between CR1 polymorphisms and LOAD risk was estimated by odds ratios (ORs) and their 95% confidence intervals (CIs). A total of 6 articles were eventually identified with 2752 LOAD cases and 2313 controls for the rs6656401 polymorphism, and 4 studies containing 2547 LOAD cases and 2338 controls were included for the rs3818361 polymorphism. Overall, the pooled data showed that the CR1 rs6656401 polymorphism was significantly associated with LOAD risk in the overall population (A vs. G: OR=1.32, 95%CI=1.17-1.50, P=0.000; AG+AA vs. GG: OR=1.39, 95%CI=1.20-1.61, P=0.000). With respect to the CR1 rs3818361 polymorphism, a statistically significant increased LOAD risk was observed in the overall population (T vs. C: OR=1.24, 95% CI=1.13-1.37, P=0.000; TT+TC vs. CC: OR=1.30, 95% CI=1.15-1.46, P=0.000; TT vs. TC+CC: OR=1.35, 95% CI=1.06-1.71, P=0.014). This meta-analysis demonstrated significant associations of both the CR1 rs6656401 and CR1 rs3818361 polymorphisms with LOAD susceptibility.

Meta-analysis: diagnostic value of serum anti-mutated citrullinated vimentin antibodies in patients with rheumatoid arthritis

Conventional tests are not always helpful in making a diagnosis of rheumatoid arthritis (RA). This study aimed to comprehensively and quantitatively summarize the evidence on the accuracy of anti-mutated citrullinated vimentin (MCV) assay in the diagnosis of RA. A comprehensive meta-review of data on the accuracy of MCV concentrations in the diagnosis of RA were carried out from 16 published studies. Furthermore, receiver operating characteristic curves were used to summarize the overall test performance. The summary estimates for MCV in the diagnosis of RA were: sensitivity 0.77 [95% confidence interval (CI) 0.75–0.78], specificity 0.89 (95% CI 0.87–0.90), positive likelihood ratio (LR+) 7.24 (95% CI 5.60–9.36), negative likelihood ratio (LR−) 0.28 (95% CI 0.23–0.34) and diagnostic odds ratio 29.66 (95% CI 21.09–41.71). The area under the summary receiver operating characteristic curves was 0.92. Data from meta-analysis suggest the accuracy of MCV assay in the diagnosis of RA is high, but ultimately clinician must consider the results of MCV tests combing with other conventional examinations and the clinical feature.

Quantitative assessment of CYP2D6 polymorphisms and risk of Alzheimer's disease: a meta-analysis.

BACKGROUND CYP2D6 gene encoding CYP2D6 enzyme belonging to the cytochrome P450 system has aroused long attention being a candidate gene for Alzheimers disease (AD), but the results remain inconsistent and underpowered. OBJECTIVES To investigate the contradictory results, the effect of single CYP2D6 polymorphism- CYP2D6*4, together with CYP2D6 phenotypes on the risk of AD, was evaluated using a meta-analysis. METHODS Electronic database search of PubMed, Embase and Cochrane Library was conducted up to Apr 17, 2014. Odds ratio (OR) along with the 95% confidence interval (CI) was calculated. Subgroup analysis was performed to examine the impact of CYP2D6 variants on different ethnic. Meta-regression was performed to explore possible source of heterogeneity. RESULTS A total of 11 studies involving 643AD cases and 1375 controls were included for CYP2D6*4 polymorphism, and 4 studies consisted of 411AD cases and 603 controls were included for CYP2D6 phenotypes. With respect to CYP2D6*4 polymorphism, significantly increased risk of AD was found in allelic contrast model of A vs. G (OR=1.29, 95%CI=1.03-1.62, P=0.026), co-dominant genetic model AA vs. GG (OR=1.91, 95%CI=1.04-3.51, P=0.038); and recessive genetic model AA vs. AG+GG (OR=1.88, 95%CI=1.03-3.46, P=0.041) in the overall populations. Similar results were also indicated in subgroup analysis in Caucasians. As for CYP2D6 phenotypes, no significant association with AD was revealed. CONCLUSIONS Our data support that the CYP2D6*4 polymorphism but not CYP2D6 phenotypes might be associated with increased AD risk, particularly in Caucasian populations.