Prognostic alternative mRNA splicing signature in hepatocellular carcinoma: a study based on large-scale sequencing data.

Most genes are alternatively spliced and increasing number of evidences show that alternative splicing (AS) is modified and related to tumor progression. Systematic profiles of AS signature in hepatocellular carcinoma (HCC) is absent and urgently needed. Here, differentially spliced AS transcripts between HCC and non-HCC tissues were compared, prognosis-associated AS events by using univariate Cox regression analysis were selected. Our gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognostic AS signatures were then constructed for HCC prognosis prediction by Lasso regression model. We also analyzed splicing factors (SFs) regulating underlying mechanisms by Pearson correlation and then built corresponding regulatory networks. In addition, we explored the performance of AS signature in the mutated HCC samples. Genome-wide AS events in 377 HCC patients from TCGA were profiled. Among 34 163 AS events in 8985 genes, 3950 AS events in 2403 genes associated with overall survival (OS) significantly for HCC were detected. In addition, computational algorithm results showed that metabolic and ribosome pathways may be the potential molecular mechanisms regulating the poor prognosis. More importantly, survival-associated AS signatures revealed high performance in predicting HCC prognosis. The area under curve for AS signature was 0.806 in all HCC and 0.944 in TP53 mutated HCC samples at 2000 days of OS. We submitted prognostic SFs to build the AS regulatory network, from which we found prognostic AS events were significantly enriched in metabolism-related pathways. A robust AS signature for HCC patients and revealed the regulatory splicing networks contributing to the potential significantly enriched metabolism-related pathways.

Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population.

BACKGROUND AND AIM: Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated. MATERIALS AND METHODS: In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings. RESULTS: We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSION: These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.

[Implanting the edentulous jaws with "All-on-4" immediate reconstruction: a preliminary clinical observation].

OBJECTIVE: To evaluate the treatment outcome of the "All-on-4" immediate loading protocol via survival rate of the implants,survival rate of the prosthesis,marginal bone, postoperative complications and patient satisfaction. METHODS: In our study, 40 patients with 49 edentulous jaws (31 mandibles and 18 maxillae) were enrolled. Each jaw was restored by the shortened dental arch prosthesis supported by only 4 implants according to the All-on-4 protocol (All-on-4, Nobel Biocare AB, Goteborg, Sweden). For all the patients enrolled in the study, the loading was applied within 12 hours of surgery. The provisional prosthesis could be replaced by the final restorations within 6 to 12 months. In the present study, the survival rate of the both implants and restorations were calculated and analyzed. The radiographic evaluation of marginal bone level changes was measured. The values of the marginal bone level changes of the angled and axial implants were analyzed by the statistic software. RESULTS: In the present study, totally 196 implants were inserted, of which 13 implants failed during the whole following up periods, with 11 implants of the maxillae and 2 of the mandibles. The survival rate of the prosthesis was 95.9% (47/49). The implant survival rate of the maxillae was 85.5% (65/76)while that for the mandibles was 98.3%(118/120). The implant survival rate of the angled implants was 91.8% (90/98), while that for the straight implants was 95.0% (93/98). No significant difference in marginal bone loss was found between angled and axial implants in the 12-month evaluation according to the Wilcoxon rank sum test (P>0.05). During the follow-up period,mechanical complications as fracture of the provisional prostheses, loose of the retain screw, or crack of the artificial teeth were found in 20 prostheses. CONCLUSION: The present preliminary data of the short term observation suggest that the "All-on-4" immediate loading protocol is a viable treatment modality for the edentulous jaws. However, long term clinical random controlled trials with large samples are still needed to confirm the validity of the technique.

Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations.

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

TNF-308 gene polymorphism and tuberculosis susceptibility: a meta-analysis involving 18 studies.

A number of studies have investigated the association between TNF-308 (rs1800629 G/A) polymorphisms and the susceptibility towards tuberculosis (TB) in different populations. However, many of these studies provided inconsistent results. In this study, a systematic review and meta-analysis of the published studies was performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science and CNKI databases were searched for case-control studies published up to Jan 2011, we used no lower date limit. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 18 publications from 2001 to 2010, involving 2584 TB cases and 3817 controls were included. Overall, for the A allele carriers (G/A + A/A) vs. homozygote GG, the pooled OR was 1.03 (95% CI = 0.89-1.19; P = 0.912 for heterogeneity). For the allele A vs. allele G, the pooled OR was 1.07 (95% CI = 0.93-1.22; P = 0.013 for heterogeneity). In the stratified analysis by ethnicity, among Asians significant risk was found for allele A vs. allele G (OR = 1.22, 95% CI = 1.02-1.47; P = 0.152 for heterogeneity), no significant risks were found among Caucasians. This meta-analysis indicated that the TNF-308 polymorphism was not associated with the risk of TB in the total population, however the significant risk for TNF-308 A allele was found among Asians not Caucasians.

[Influence of the placing depth of implants with platform switching on the marginal bone level in the posterior mandible: a clinical study].

OBJECTIVE: The purpose of this study was to evaluate the influence of the placing depth of the implants with platform switching (Ankylos) on the marginal bone remodeling, by means of radiological observation. METHODS: 111 Ankylos implants in the posterior mandible from 46 patients (20 male and 27 female) were enrolled in this study. Followed up by 58.1 months on average (from 36 to 85), 222 mesial and distal sites of these implants were evaluated by means of measuring the level of the marginal bone (LMB) on the panoramic radiograph. RESULTS: Among these 111 successfully functional loaded implants, there were no significant differences with the marginal bone absorption values, no matter the implants were placed below, at, or above the bone level (P>0.05). Concerning the stabilization of the marginal bone, when placed below the bone level, 67.7% of the implant sites had their LMBs stabilized at or above the implant platform, and 23.3% absorbed vertically, respectively 19.7% and 80.3% when placed at the bone level, with significant difference (P<0.001). CONCLUSION: Based on a long-term (over 3 years) observation, the implants placed below, as compared to at or above, the alveolar crest level, might have more chance to keep the marginal bone stabilized at or above the implant platform.

A Single-Visit Technique for Fabricating Interim, Immediately Loaded Implant-supported Full-arch Prostheses with Prefabricated Rigid Connecting Bars: a Case Report.

Traditional techniques for fabricating interim, immediately loaded implant-supported full-arch prostheses are complex and time-consuming. The present study presents an efficient technique for fabricating interim prostheses with prefabricated multipurpose rigid connecting bars. This technique can minimise the misfit attributed to the polymerisation shrinkage of resin and expansion of the working cast, and simultaneously facilitate impression taking and occlusal records in one visit, thus reducing laboratory and chair time. Due to its ease of use and clinical efficiency, the present technique is considered particularly beneficial for immediate loading rehabilitation.

Randomized phase II study of TX followed by XELOX versus the reverse sequence for chemo-naive patients with metastatic gastric cancer.

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. Background: Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. Methods: In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. Results: Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). Conclusion: TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX).

BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

Glutathione S-transferase T1 polymorphism is associated with breast cancer susceptibility.

The association between present/null polymorphism of glutathione S-transferase T1 (GSTT1) and breast cancer risk are still inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship. A total of 48 studies including 17,254 cases and 21,163 controls were involved in this meta-analysis. When all studies were pooled into the meta-analysis, significantly elevated breast cancer risk was associated with null genotype (OR=1.138, 95% CI=1.051-1.232). When stratified by ethnicity, significantly increased risks were found for Caucasians (OR=1.185, 95% CI=1.075-1.306), but no statistically significantly increased risks were found in Asians (OR=1.017, 95% CI=0.846-1.223) and Africans (OR=1.160, 95% CI=0.815-1.650). In the subgroup analysis by controls source, statistically significantly elevated risks were both found in population-based studies (OR=1.123, 95% CI=1.014-1.243) and hospital-based studies (OR=1.181, 95% CI=1.056-1.321). When stratified by menopausal status, no statistically significantly increased risks were found in premenopausal women (OR=1.115, 95% CI=0.925-1.345) and postmenopausal women (OR=1.077, 95% CI=0.992-1.169). In summary, this meta-analysis suggests that the GSTT1 null genotype is a risk allele for breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

miR-196a2 C allele is a low-penetrant risk factor for cancer development.

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.

The association between common genetic variant of microRNA-146a and cancer susceptibility.

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.

GSTM1 null allele is a risk factor for gastric cancer development in Asians.

Glutathione S-transferase M1 (GSTM1), which plays an important role in detoxification pathways to protect against damage caused by reactive metabolites of chemicals, has been considered as potential gastric cancer susceptibility genes. However, the published data on the association between GSTM1 present/null polymorphism and gastric cancer risk are still inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Totally, 44 studies including 5440 cases and 11607 controls were involved in the analysis. When all studies were pooled into the meta-analysis, obviously increased gastric cancer risk was found in null genotype carriers (OR=1.19, 95% CI: 1.08-1.33). When stratified by ethnicity, obviously evaluated risk was found in Asians (OR=1.31, 95% CI: 1.11-1.54) but not reached to statistically significance in Caucasians (OR=1.11, 95% CI: 0.96-1.28). In the subgroup analysis by hospital-based studies or population-based studies, statistically significantly elevated risk was found in hospital-based studies (OR=1.34, 95% CI: 1.07-1.67) but not reached to statistically significance in population-based studies (OR=1.11, 95% CI: 0.99-1.25). In summary, this meta-analysis result indicates that the GSTM1 null genotype is a low-penetrant risk factor for gastric cancer development in Asians.

BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis.

Epidemiologic studies have evaluated the association between BRAF mutations and resistance to the treatment of anti-EGFR monoclonal antibodies (MoAb) in patients with metastatic colorectal cancer (mCRC). However, the results are still inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. A total of 11 studies were included in the final meta-analysis. There were seven studies for unselected mCRC patients and four studies for patients with wild type KRAS mCRC. Among unselected mCRC patients, BRAF V600E mutation was detected in 48 of 546 primary tumors (8.8%). The objective response rate (ORR) of patients with mutant BRAF was 29.2% (14/48), whereas the ORR of patients with wild-type BRAF was 33.5% (158/472).The overall RR for ORR of mutant BRAF patients over wild-type BRAF patients was 0.86 (95% CI=0.57-1.30; P=0.48). For patients with KRAS wild-type mCRC, BRAF V600E mutation was detected in 40 of 376 primary tumors (10.6%). The ORR of patients with mutant BRAF was 0.0% (0/40), whereas the ORR of patients with wild-type BRAF was 36.3% (122/336). The pooled RR of mutant BRAF patients over wild-type BRAF patients was 0.14 (95% CI=0.04-0.53; P=0.004). In conclusion, this meta-analysis provides evidence that BRAF V600E mutation is associated with lack of response in wild-type KRAS mCRC treated with anti-EGFR MoAbs. BRAF mutation may be used as an additional biomarker for the selection of mCRC patients who might benefit from anti-EGFR MoAbs therapy.

APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis.

Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928-1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861-1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers.

TNF-308 gene polymorphism is associated with COPD risk among Asians: meta-analysis of data for 6,118 subjects.

Chronic obstructive pulmonary disease (COPD) is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The gene encoding tumor necrosis factor (TNF) is one of several candidate loci for the pathogenesis of COPD and is highly polymorphic. A number of studies have investigated the association between the TNF-308 polymorphisms and COPD risk in different populations, and resulted in inconsistent results. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science, and CNKI databases were searched for case-control studies published from 1966 to April 2009. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twenty-four eligible studies, comprising 2,380 COPD cases and 3,738 controls, were included in the meta-analysis. The pooled result showed that the TNF-308 polymorphisms were significantly associated with an increased risk of COPD (OR=1.335, 95% CI: 1.172-1.522, for allele A carriers versus G/G; OR=1.330, 95% CI=1.174-1.505, for allele A versus allele G). Subgroup analysis supported the results in the Asian populations, but not in the Caucasian populations. When the analysis was limited to only those studies in which the COPD cases and controls were smokers/ex-smokers, the pooled results supported the conclusion. This meta-analysis suggested that the TNF-308 A allele is a more significant risk factor for developing COPD among Asian populations, but not among Caucasians.

Current evidences on vascular endothelial growth factor polymorphisms and breast cancer susceptibility.

Several polymorphisms of vascular endothelial growth factor (VEGF) such as 936 C/T, -2578 C/A, -406 C/T, and -1154 G/A polymorphism have been identified. Published data on the association between VEGF polymorphisms and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude OR with 95% CI was used to assess the strength of association between them. For VEGF 936C/T polymorphism, a total of 10 studies including 7,685 cases and 7,915 controls were involved in this meta-analysis. Overall, no significant associations were found between VEGF 936C/T polymorphism and breast cancer risk when all studies pooled into the meta-analysis (TC vs. CC: OR = 0.904, 95% CI = 0.797-1.024; TT vs. CC: OR = 0.974, 95% CI = 0.786-1.205; dominant model: OR = 0.911, 95% CI = 0.811-1.024; and recessive model: OR = 0.991, 95% CI = 0.801-1.226). In the subgroup analysis by ethnicity, still no significant associations were found for all comparison models. For -2578 C/A, -406 C/T, and -1154 G/A polymorphism, there were too limited data to perform a meta-analysis. In conclusion, this meta-analysis suggests that the VEGF 936C/T polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility.

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC+AC vs. AA), and recessive model (CC vs. AC+AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR=0.99, 95% CI 0.94-1.05; CC vs. AA: OR 0.99, 95% CI 0.90-1.09; dominant model: OR=0.99, 95% CI 0.95-1.04; and recessive model: OR=0.98, 95% CI 0.90-1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

Scientific publications in anesthesiology journals from East Asia: a 10-year survey of the literature.

The scientific publications in anesthesiology research from East Asian authors have not been reported yet. The present study was designed to analyze the contribution of articles from East Asia to anesthesiology research. Articles published in 17 journals in anesthesiology originating from Japan, China, and South Korea from 2000 to 2009 were retrieved from the PubMed database and Web of Science. From 2000 to 2009, there were 3,076 articles published from East Asia. During this period, there were a notable decrease in publications from Japan and modest increases in publications from both China and South Korea. The average 5-year impact factor of the published articles was similar among the three regions, and China had the highest average number of citations to each article. Anesthesia & Analgesia published more articles than any other journal from all three regions. Our analysis showed that Japan was the most productive region in East Asia, but there was a notable decrease in publications from Japan in 2000-2009. The impact factor of the articles suggests similar levels of scholarship. Anesthesia & Analgesia was the most popular journal in East Asia.