Diabetes mellitus and the risk of sudden cardiac death: A systematic review and meta-analysis of prospective studies

Background

Although diabetes mellitus is an established risk factor for myocardial infarction and stroke, data on the association with sudden cardiac death are less extensive and the findings have not been entirely consistent. We therefore conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and risk of sudden cardiac death.

Diabetes mellitus,blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies

Background and Aim

The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis.

Safety and efficacy of transdermal buprenorphine for the relief of cancer pain

Purpose

This study aimed to synthesize the available evidence on the efficacy and safety of transdermal (TD) buprenorphine.

Methods

We searched studies in electronic databases. Randomized controlled trials (RCTs) assessing the efficacy of TD buprenorphine comparing with placebo or other comparator drug in relieving cancer pain were included. The primary end points are patient-reported pain intensity and pain relief. For dichotomous data, the summary relative risk (RR) and its 95 % confidence interval (CI) were derived using random-effect model in view of heterogeneity testing.

Results

Eight clinical trials (n = 909) were included in the analysis. Only a few studies reported the same outcome in similar way, which created difficulty in the pooling of outcome data. Two studies (n = 288) assessed ‘responders’ and showed a significant difference between TD buprenorphine and placebo in all three doses of TD buprenorphine, 35.5, 52.5, or 70 μg/h (RR 1.74, 95 % CI 1.31–2.32; I ² 0 %); the numbers-needed-to-treat was 5.8 (3.9–11). Two studies (n = 331) showed a comparable requirement for rescue SL buprenorphine between TD buprenorphine and placebo (RR 1.25, 95 % CI 0.84–1.88; I ² 0 %). The preferred outcome measure ‘50 % pain relief’ was not reported in any included studies. On the basis of summary quality, further research is likely to have an important impact on our confidence in the estimate.

Conclusion

Transdermal buprenorphine has an increasing role for the relief of cancer pain. Further research in this field is needed. Multicentre studies in this field using a common protocol and strict supervision will be more practicable.     

Meat Consumption Is Associated with Esophageal Cancer Risk in a Meat- and Cancer-Histological-Type Dependent Manner

Background

We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer.

Aims

The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer.

Methods

We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case–control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case–control studies were included.

Results

The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98–1.46) for total meat, 1.55 (95 % CI 1.22–1.96) for red meat, 1.33 (95 % CI 1.04–1.69) for processed meat, 0.72 (95 % CI 0.60–0.86) for white meat, 0.83 (95 % CI 0.72–0.96) for poultry, and 0.95 (95 % CI 0.76–1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat.

Conclusions

Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer.     

Increased Risk of Second Lung Cancer in Hodgkin’s Lymphoma Survivors: A Meta-analysis

Background

Patients treated for Hodgkin’s lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. The aim of this meta-analysis was to quantify such risk and to analyze contributing risk factors in HL survivors.

Methods

According to predefined selection criteria, a literature search identified 21 studies that were included in the analysis.

Results

After eliminating overlapping or duplicate data, 793 (76 % males) incidences of SLC were encountered in 74,831 patients (58 % males) with HL over a median follow-up of 11.5 years. The median age at HL diagnosis and the median age at SLC diagnosis were 33.0 and 45.9, respectively. The mean latency between treatment of HL and development of SLC was 11.5 years. The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18–6.70], I ² = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. RR was positively related to study size, male-to-female ratio, institutional versus population-based data sets, and the use of any radiotherapy (RT) or combined modality therapy (CMT), while age at diagnosis of HL was not significant. The highest risk was shown among patients aged 15–24 years (RR = 8.76 [95 % CI, 4.55–16.89]), while the lowest risk occurred in patients ≥55 years at primary treatment (RR = 2.88 [95 % CI, 2.33–3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10–14 years (RR = 4.17 [95 % CI, 3.62–8.81]), but did not increase after ≥15 years (RR = 4.01 [95 % CI, 2.68–5.98]). RT only, CMT, or chemotherapy only was associated with RR (95 % CI) of 4.88 (3.14–7.60), 5.15 (4.08–6.50), and 2.39 (1.60–3.55), respectively. Patients with SLC demonstrated poor prognosis.

Conclusions

The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.     

Treatment outcomes of transcatheter arterial chemoembolization combined with local ablative therapy versus monotherapy in hepatocellular carcinoma: a meta-analysis

Purpose

To evaluate the effectiveness comparing the combination of TACE with local ablative therapy and monotherapy on the treatment of HCC using meta-analytical techniques.

Methods

Randomized controlled trials and clinical studies comparing TACE plus local ablative therapy with monotherapy for HCC were included in this meta-analysis. Response rate, 1-, 2-, 3-, and 5-year survival rate, and overall survival (OS) were analyzed and compared.

Results

Eighteen studies included a total of 2,120 patients with HCC 1,071 and 1,049 patients for treatment with combination therapy and monotherapy, respectively. The combination therapy group had a significantly better survival in terms of 1-, 2-, 3-, and 5-year survival rate (RR 1.10, 95 % CI 1.03–1.18, P = 0.005; RR 1.20, 95 % CI 1.10–1.30, P < 0.0001; RR 1.43, 95 % CI 1.18–1.73, P < 0.0001; RR 1.40, 95 % CI 1.22–1.61, P < 0.0001, respectively), OS (HR 0.66, 95 % CI 0.51–0.85, P = 0.001), and response rate (RR 1.54, 95 % CI 1.09–2.18, P = 0.013) than that monotherapy group in patients with HCC.

Conclusions

The meta-analysis indicates that the combination of TACE with local ablative therapy was superior to monotherapy in the treatment for patients with HCC.     

Comparison of short- and long-term outcomes after extralevator abdominoperineal excision and standard abdominoperineal excision for rectal cancer: a systematic review and meta-analysis

Purpose

Whether the introduction of extralevator abdominoperineal excision (ELAPE) improves survival and safety remains controversial. We conducted a systematic review and meta-analysis of all comparative studies to define the efficacy and safety of ELAPE and standard abdominoperineal excision (APE).

Materials and methods

A search for all major databases and relevant journals from inception to July 2013 without restriction on languages or regions was performed. Outcome measures were the oncological parameters of circumferential resection margin (CRM) involvement, intraoperative bowel perforation (IOP), and local recurrence, as well as other parameters of blood loss, operative time, length of hospitalization, and postoperative complication. The test of heterogeneity was performed with the Q statistic.

Results

A total of 949 patients were included in the meta-analysis. Oncological pooled estimates of intraoperative bowel perforation rate (RR 0.34; 95 % CI 0.21–0.54; P < 0.00001), CRM involvement (RR 0.44; 95 % CI 0.34–0.56; P < 0.00001), and local recurrence (RR 0.32; 95 % CI 0.14–0.74; P = 0.008) all showed outcomes that were significantly lower in ELAPE than in APE. A similar incidence of postoperative complication was attributed to both groups, including overall complication (RR 0.93; 95 % CI 0.66–1.32; P = 0.69), perineal wound complication (RR 0.72; 95 % CI 0.33–1.55; P = 0.39), and urinary dysfunction (RR 1.53; 95 % CI 0.88–2.67; P = 0.13).

Conclusion

ELAPE has a lower intraoperative bowel perforation rate, positive CRM rate, and local recurrence rate than APE. There is evidence that in selected low rectal cancer patients, ELAPE is a more efficient and equally safe option to replace APE. Due to the inherent limitations of the present study, future randomized controlled trials will be useful to confirm this conclusion.     

Obstructive sleep apnea increases the risk of cardiac events after percutaneous coronary intervention: a meta-analysis of prospective cohort studies

Purpose

Recent studies have shown an association between obstructive sleep apnea (OSA) and coronary artery disease; however, the association between OSA and cardiac outcomes in patients after percutaneous coronary intervention (PCI) remains undetermined.

Methods

PubMed, EMBASE, and CENTRAL were searched from inception to July 2016 for cohort studies that followed up with patients after PCI, and evaluated their overnight sleep patterns within 1 month for major adverse cardiac events (MACEs) as primary outcomes including cardiac death, non-fatal myocardial infarction (MI), and coronary revascularization and secondary outcomes including re-admission for heart failure and stroke. Outcomes data were pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the I ² statistics. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual investigation of funnel plots.

Results

We identified seven pertinent studies including 2465 patients from 178 related articles. OSA was associated with MACEs (odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20–1.93, I ² = 29%), which included cardiac death (OR 2.05, 95% CI, 1.15–3.65, I ² = 0%), non-fatal MI (OR 1.59, 95% CI, 1.14–2.23, I ² = 15%), and coronary revascularization (OR 1.69, 95% CI, 1.28–2.23, I ² = 0%). However, OSA was not associated with re-admission for heart failure (OR 1.71, 95% CI, 0.99–2.96, I ² = 0%) and/or stroke (OR 1.68, 95% CI, 0.91–3.11, I ² = 0%) according to the pooled results.

Conclusions

In patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal MI, and coronary revascularization.

     

Fasting blood glucose and risk of prostate cancer: A systematic review and meta-analysis of dose-response

Aim

This study aimed to test the dose-response relationship between fasting blood glucose (FBG) levels and risk of prostate cancer.

Influence of cardioversion on asymptomatic cerebral lesions following atrial fibrillation ablation

Purpose

Asymptomatic cerebral lesions detected by diffusion-weighted magnetic resonance imaging (MRI) following atrial fibrillation (AF) ablation were reported in recent years. It was reported that cardioversion during the procedure of AF ablation was one independent risk factor of asymptomatic cerebral lesions. However, in some studies, the similar association between asymptomatic cerebral lesions and intraprocedural cardioversion was not observed. Given the inconsistent results, we did a meta-analysis to explore the influence of intraprocedural cardioversion on the asymptomatic cerebral lesions detected by MRI following AF ablation.

Methods

Studies exploring the association between cardioversion during AF ablation and asymptomatic cerebral lesions following AF ablation were systematically searched in PubMed, Web of Science and the Cochrane Library Databases. Odds ratios (ORs) and 95 % confidence intervals (CIs) were pooled. Subgroup and sensitivity analyses were performed to explore the source of heterogeneity.

Results

Nine studies involving 813 participants were included in the present meta-analysis. When we pooled data from nine studies using fixed-effects model, we found cardioversion during the procedure significantly increased the risk of asymptomatic cerebral lesions detected by MRI following AF ablation (pooled OR?=?1.793, 95 % CI 1.201–2.678, I ²?=?38.8 %, P _{heterogeneity}?=?0.109).

Conclusions

Cardioversion during AF ablation significantly increased the risk of asymptomatic cerebral lesions on MRI following the procedure. Additional studies are required to further verify the association.     

Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis

Purpose

A variety of studies have been performed to elucidate the polymorphisms in promoter regions of matrix metalloproteinases (MMPs) associated with the risk of digestive cancers, and yet, results remain conflicting and heterogeneous. Thus, we undertook a systematic meta-analysis to determine the genetic susceptibility of MMPs to digestive cancers.

Methods

A computerized literature search was conducted in databases of PubMed, Embase, and ISI Web of Knowledge till October 2012 for any MMP genetic association study in oral squamous, gastric, esophageal, and colorectal carcinomas. Odds ratios (OR) and 95 % confidence interval (CI) were estimated for each gene under dominant and recessive models, and the heterogeneity between studies was assessed using Q test and I ² value. Overall and subgroup analysis according to anatomical sites and ethnicity was carried out. Statistical analysis was performed with Review Manager 5.0.

Results

A total of 40 eligible publications with 68 comparisons were included in this study. For MMP1 nt-1607, individuals with 2G state could increase risk of digestive cancers in total analysis (dominant: OR = 1.31, 95 % CI = 1.16–1.48, P < 0.00001; recessive: OR = 1.29, 95 % CI = 1.11–1.50, P = 0.0009). In the subgroup of tumor sites, significant associations were also observed in esophageal cancer and colorectal cancer under both genetic models. For MMP2 nt-1306, CT or TT carriers performed significant protection against digestive cancer in the dominant model (OR = 0.69, 95 % CI = 0.55–0.85, P = 0.0007) of the overall. In the subgroup analysis, significant association was found in esophageal cancer, with borderline effects in gastric cancer and oral squamous cell carcinoma. For MMP7 ?181 A/G, significant association was observed under two genetic models in the overall (dominant: OR = 1.26, 95 % CI = 1.10–1.43, P = 0.0009; recessive: OR = 1.33, 95 % CI = 1.11–1.60, P = 0.002) and in the individual cancer subgroup of esophageal cancer and gastric cancer. For MMP9 ?1,562 C/T, a borderline effect was found with digestive cancers in the total and stratified analysis of the colorectal cancer under dominant model. No association was observed in either the overall or subgroup analysis for MMP3 ?1,171 5A/6A.

Conclusions

Our meta-analysis demonstrated the fact that polymorphisms in promoter regions of MMP genes might be related to the susceptibility of digestive cancers, with cancer development for MMP1 and MMP7, and a protection against cancer for MMP2 and MMP9. Further evidences with adequate sample sizes need to be conducted.     

A systematic review and meta-analysis of comparative studies on the efficacy of extended pelvic lymph node dissection in patients with clinically localized prostatic carcinoma

Purpose

Pelvic lymph node dissection (PLND) has been performed during radical prostatectomy in nearly all patients with clinically localized prostatic carcinoma (PCa), while the specific regions that needed to be removed demonstrated bifurcation among urologist. However, clinical studies comparing extended PLND (ePLND) with standard PLND (sPLND) and limited PLND (lPLND) reveal conflicting, or even opposing results.

Methods

All controlled trials comparing ePLND with sPLND or lPLND were identified through comprehensive searches of the PubMed, Cochrane Library and Embase databases. A systematic review and meta-analysis of these studies were then performed.

Results

Eighteen studies with a total of 8,914 patients were included. Regardless of being compared with sPLND or lPLND, ePLND significantly improved LN retrieval [ePLND vs. sPLND: weighted mean difference (WMD) 11.93, 95 % confidence interval (CI) 9.91–13.95, p < 0.00001; ePLND vs. lPLND: WMD 8.27, 95 % CI 3.53–13.01, p = 0.0006] and the detection of more LNs positive of metastasis [risk ratio (RR) 3.51, 95 % CI 2.14–5.75, p < 0.00001; RR 3.50, 95 % CI 2.20–5.55, p < 0.00001, respectively]. EPLND decreased the complication rate, but the differences were not statistically significant (RR 1.52, 95 % CI 0.87–2.65, p = 0.14; RR 1.52, 95 % CI 0.67–3.45, p = 0.32, respectively). Operating time, estimated blood loss, length of hospital stay and biochemical recurrence (BCR) were statistically insignificant between techniques.

Conclusions

ePLND shows benefits associated with increased LNs yield, LNs positivity, and safety, significantly with no risk of side effects. However, ePLND did not decrease BCR. Additional high-quality, well-designed randomized controlled trials and comparative studies with long-term follow-up results are required to define the optimal procedure for patients with clinically localized PCa.     

Meta-Analysis: The Association Between HIV Infection and Extrapulmonary Tuberculosis

Background

Extrapulmonary tuberculosis has been an AIDS-defining condition. Individual studies that highlight the association between HIV and extrapulmonary TB are available. Our objectives were to synthesis evidence on the association between extrapulmonary tuberculosis and HIV and to explore the effective preventive measures of these two diseases.

Methods

This is a meta-analysis of observational studies reporting effect estimates on how HIV is associated with extrapulmonary tuberculosis. We searched for the eligible studies in the electronic databases using search terms related to HIV and extrapulmonary tuberculosis. Where possible, we estimated the summary odds ratios using random effects meta-analysis. We stratified analysis by the type of study design. We assessed heterogeneity of effect estimates within each group of studies was assessed using I ² test.

Results

Nineteen studies (7 case control studies and 12 cohort studies) were identified for the present study. The pooled analysis shows a significant association between HIV and extrapulmonary tuberculosis (summary odds ratio: 1.3; 95 % confidence interval (CI) 1.05–1.6; I ²: 0 %). In a subgroup analysis with two studies, a significant association was found between CD4+ count less than 100 and the incidence of extrapulmonary tuberculosis (summary OR: 1.31; 95 % CI 1.02–1.68; I ²: 0 %).

Conclusions

Findings show evidence on the association between extrapulmonary tuberculosis and HIV, based on case control studies. Further studies to understand the mechanisms of interaction of the two pathogens are recommended.     

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene

Background

Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

Methods

The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

Results

The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09–2.05, p = 0.012; and OR 1.51, 95 % CI 1.09–2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10–2.17, p = 0.013; and OR 1.56, 95 % CI 1.10–2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01–2.21, p = 0.044; and OR 1.52, 95 % CI 1.03–2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28–5.43, p = 0.009; and OR 4.35, 95 % CI 1.93–9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41–12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08–2.85, p = 0.04).

Conclusion

This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.     

Breastfeeding and the maternal risk of type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

Background and aimsBreastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose–response meta-analysis of breastfeeding and maternal risk of type 2 diabetes.Methods and resultsWe conducted a systematic review and dose–response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57–0.82, I² = 75%, p_{heterogeneity} = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77–1.04, I² = 93%, p_{heterogeneity} < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86–0.96, I² = 81%, p_{heterogeneity} = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p_nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels.ConclusionThis meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes.     

Association between survivin -31G>C polymorphism and cancer risk: meta-analysis of 29 studies

Purpose

A growing body of evidence has shown the possible relevance of survivin -31G>C (rs9904341) promoter polymorphism to the genetic susceptibility of cancer. Because of the lack of available conclusive data, we performed a meta-analysis of all relevant available studies to derive a more precise estimation of the relationship.

Methods

A comprehensive literature search of Medline electronic database was conducted to collect relevant studies until August 18, 2013. References of the retrieved articles were also screened. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.2 software.

Results

A total of 29 studies with 7,473 cancer cases and 9,086 controls were included in the meta-analysis. Overall, the pooled analysis revealed that suvivin -31G>C polymorphism was significantly associated with increased cancer risk under multiple genetic models (CC vs. GG: OR = 1.37, 95 % CI 1.06–1.76; CC vs. CG: OR = 1.27, 95 % CI = 1.10–1.46; CC vs. CG + GG: OR = 1.31, 95 % CI = 1.10–1.57). In subgroup analysis with different cancer types, the -31G>C polymorphism significantly increased the risk of colorectal, gastric, and urothelial cancers, while this SNP remarkably decreased the susceptibility to hepatocellular carcinoma. Further stratification analysis by ethnicity showed an increasing cancer risk in the Asian population (CC vs. GG: OR = 1.61, 95 % CI 1.17–2.21; CC vs. CG: OR = 1.31, 95 % CI 1.12–1.53; CC vs. CG + GG: OR = 1.43, 95 % CI 1.16–1.77) but not in Europeans.

Conclusions

The survivin -31G>C polymorphism is associated with elevated cancer risk, especially among colorectal, gastric, and urothelial cancers and Asian populations.     

Association of CYP1B1 Leu432Val Polymorphism and Lung Cancer Risk: An Updated Meta-Analysis

Background

Cytochrome P4501B1 (CYP1B1) a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. Impacts on the catalytic activity of the CYP1B1 enzyme, as well as an association of the Leu432Val polymorphism with the risk of lung cancer, have been described; however, the results remain controversial.

Methods

We conducted a meta-analysis of all available studies to clarify the effects of the Leu432Val polymorphism on lung cancer risks basing on 2,543 lung cancer cases and 3,304 controls from ten separate comparisons. We also performed subgroup analyses by ethnicity (categorized as Caucasian, Asian and African-American), gender, smoking status ,and histological type. A pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to estimate the strength of the association.

Results

A significantly increased risk was found in our meta-analysis in the overall population (Val/Val vs. Leu/Leu: OR = 1.371, 95 % CI 1.137–1.652, P = 0.001). In subgroup analysis, significant associations with lung cancer susceptibility were also found in Caucasians (Val/Val vs. Leu/Leu: OR = 1.312, 95 % CI 1.075–1.602, P = 0.008), females (Val/Val vs. Leu/Leu: OR = 1.472, 95 % CI 1.097–1.976, P = 0.010), and smokers (dominant model Leu/Val + Val/Val vs. Leu/Leu: OR = 1.257, 95 % CI 1.016–1.554, P = 0.035). Null results were noted in the subgroup analysis by histological type under different genetic models.

Conclusions

Our results suggest that the CYP1B1 Leu432Val polymorphism acts as a risk factor for the carcinogenesis of lung cancer.     

Genetic association of osteopontin (OPN) and its receptor CD44 genes with susceptibility to Chinese gastric cancer patients

Purpose

(1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor—cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer.

Methods

We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC).

Results

We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10^?4, odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511–0.808 and P = 1.59 × 10^?4, OR 0.642, 95 %CI 0.510–0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008–1.622 and P = 0.047, OR 1.334, 95 % CI 1.003–1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127–0.926 and P = 0.029, OR 0.343, 95 %CI 0.127–0.926) and OPN rs1126772 revealed associations with tumor–node–metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073–2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049–2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r _s = 0.164).

Conclusions

We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.     

Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer

Background

Peroxisome proliferator-activated receptors (PPAR) are implicated in pathogenesis of insulin resistance and cancers of the digestive system.

Aim

We investigated the associations of single nucleotide polymorphisms (SNPs) of PPAR δ and γ with gastric cancer and explored interactions with risk factors of gastric cancer.

Methods

We conducted our analysis in a case–control study of 196 gastric cancer patients and 397 controls residing in the Taixing region of Jiangsu, China. Six SNPs in the PPARδ (rs2076167, rs3734254) and PPARγ genes (rs10865710, rs1801282, rs3856806, rs13306747) were genotyped. We employed logistic regression to evaluate the association between each genotype and gastric cancer and tested for gene–environment interaction with Helicobacter pylori (H. pylori) infection, smoking status, and meat and salt intake.

Results

We found that the G/G variant rs2076167, in tight linkage disequilibrium with rs3734254 (R ² = 0.97), was associated with increased risk of gastric cancer in a recessive model (OR 2.20, 95 % CI 1.12, 4.32). The association between G/G variant of rs2016167 and gastric cancer was particularly strong among those with higher salt intake (OR 5.11, 95 % CI 1.11, 23.5), but did not vary by H. pylori infection or smoking status.

Conclusion

We found that genetic variants of PPARδ were associated with gastric cancer. If the association is confirmed in larger studies, it may implicate a role for PPARδ activators, such as insulin-sensitizing agents, in prevention of gastric cancer.     

Bleeding of New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

Purpose

Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are new oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). We systematically reviewed their risk of major bleeding and efficacy in thromboembolism reduction in AF.

Methods

Eligible randomized controlled trials evaluating NOACs for stroke prevention in AF patients were identified from a systematic search of MEDLINE, EMBASE and the Cochrane database. Risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a Mantel-Haenzel random-effects model.

Results

A total of 13 studies (n?=?61,406) were included. Oral direct factor Xa inhibitors were more effective in reducing stroke and systemic embolism compared to controls (RR 0.71, 95 % CI 0.54–0.92, P?=?0.009) or vitamin K antagonists (VKAs) (RR 0.84, 95 % CI 0.74–0.94, P?=?0.002), with no significant difference in major and clinically relevant non-major (CRNM) bleeding (against controls: RR 0.94, 95 % CI 0.75–1.18, P?=?0.60; against VKAs: RR 0.90, 95 % 0.69–1.17, P?=?0.44). Oral direct thrombin inhibitors were associated with an improved major and CRNM bleeding profile (both comparisons: RR 0.88, 95 % CI 0.78–0.98, P?=?0.02) and a significant reduction in stroke and systemic embolism (against controls: RR 0.79, 95 % CI 0.66–0.93, P?=?0.006; against VKAs: RR 0.78, 95 % CI 0.66–0.93, P?=?0.006).

Conclusions

Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are more effective in reducing stroke and systemic embolism without increasing the risk of major bleeding compared to traditional oral anticoagulants. This favorable risk-benefit balance should be further confirmed by long-term, large-scale safety studies.