Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes.

Despite advances in genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein level information. Formalin-fixed paraffin-embedded (FFPE) tissue specimens with extended clinical outcomes are widely available. Here, we perform comprehensive proteomic profiling of 300 FFPE breast cancer surgical specimens, 75 of each PAM50 subtype, from patients diagnosed in 2008-2013 (n = 178) and 1986-1992 (n = 122) with linked clinical outcomes. These two cohorts are analyzed separately, and we quantify 4214 proteins across all 300 samples. Within the aggressive PAM50-classified basal-like cases, proteomic profiling reveals two groups with one having characteristic immune hot expression features and highly favorable survival. Her2-Enriched cases separate into heterogeneous groups differing by extracellular matrix, lipid metabolism, and immune-response features. Within 88 triple-negative breast cancers, four proteomic clusters display features of basal-immune hot, basal-immune cold, mesenchymal, and luminal with disparate survival outcomes. Our proteomic analysis characterizes the heterogeneity of breast cancer in a clinically-applicable manner, identifies potential biomarkers and therapeutic targets, and provides a resource for clinical breast cancer classification.

[Hypoxic stimulation leads to the changes of inflammatory factors in mucosal epithelial cells of nasal polyps].

Objective: To investigate the roles of hypoxic stimulation in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing the variation and differences of inflammatory factors secreted from epithelial cells of nasal polyps and normal nasal mucosa under hypoxic stimulation. Methods: Sixty-eight patients who were diagnosed with CRSwNP from June 2015 to January 2018 at China-Japan Union Hospital of Jilin University were analyzed, including 36 males and 32 females, aged (45.2±12.5) years. Nasal polyps mucosa was included in CRS-NP group and inferior turbinate mucosa was included in CRS-IT group. According to the degree of eosinophil infiltration in histopathologic results, each of these two groups was further divided into eosinophil infiltration and non-eosinophil infiltration as Eos-NP group (n=34), Non-Eos-NP group (n=34), Eos-IT group (n=20) and Non-Eos-IT group (n=20). The inferior turbinate mucosa of twenty-five patients who were diagnosed with cyst of paranasal sinus or deviation of nasal septum was classified as control group (n=25), including 14 males and 11 females, aged (42.8±10.2) years. The expression of interleukin 17A (IL-17A), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in each group was analyzed by immunohistochemical staining. After 0, 24 and 48 h hypoxic stimulation, the secretion of IL-17A, IFN-γ, TNF-α in primary nasal mucosa epithelial cells of each group was tested by enzyme-linked immune sorbent assay (ELISA) experiment; the expression of HIF-1α was tested by immunofluorescent staining and imaging and Western blot. SPSS 17.0 software and two-way ANOVA were used for statistical analysis. Results: Immunohistochemical staining showed that the expression of IL-17A and TNF-α was much higher in control group (optical density (OD) value was 0.37±0.03, 0.53±0.02, respectively) and the expression of IFN-γ and HIF-1α was much higher in Eos-IT group (OD value was 0.47±0.03, 0.39±0.02, respectively). The secretion of IL-17A and TNF-α was much lower in control group than that in other groups under normal condition. After 48 h hypoxic stimulation, the secretion of IL-17A and TNF-α was much higher in control group compared with other groups. The secretion of IFN-γ in Eos-NP group was much higher than that in control group under normal condition ((13.7±1.3) pg/ml vs (11.1±1.6) pg/ml, P<0.05). After 48 h hypoxic stimulation, there was no difference of IFN-γ between control group and Eos-NP group. The expression of HIF-1α decreased in Eos-NP group and Non-Eos-NP group while increased in CRS-IT group and control group upon prolonged exposure to hypoxia. HIF-1α was mostly located at cytoplasm of epithelial cells in control and CRS-IT group while mainly located at nucleus of epithelial cells in CRS-NP group. Conclusions: The secretion of IL-17A, TNF-α, IFN-γ and the expression of HIF-1α show significant difference between normal nasal mucosa, polyps and inferior turbinate of CRSwNP under hypoxic stimulation, presenting different subcellular localization. This illustrates the proteins above are involved in transcription and regulation of the gene responsible for the pathogenesis of CRSwNP.

A Rapid and Cost-Effective Gene Expression Assay for the Diagnosis of Well-Differentiated and Dedifferentiated Liposarcomas.

Histologic examination neither reliably distinguishes benign lipomas from atypical lipomatous tumor/well-differentiated liposarcoma, nor dedifferentiated liposarcoma from other pleomorphic sarcomas, entities with different prognoses and management. Molecular confirmation of pathognomonic 12q13-15 amplifications leading to MDM2 overexpression is a diagnostic gold standard. Currently the most commonly used assay for this purpose is fluorescence in situ hybridization (FISH), but this is labor intensive. This study assessed whether newer NanoString-based technology could allow for more rapid and cost-efficient diagnosis of liposarcomas on standard formalin-fixed tissues through gene expression. Leveraging large-scale transcriptome data from The Cancer Genome Atlas, 20 genes were identified, most from the 12q13-15 amplicon, that distinguish dedifferentiated liposarcoma from other sarcomas and can be measured within a single NanoString assay. Using 21 cases of histologically ambiguous low-grade adipocytic tumors with available MDM2 amplification status, a machine learning-based analytical pipeline was built that assigns a given sample as negative or positive for liposarcoma based on quantitative gene expression. The effectiveness of the assay was validated on an independent set of 100 sarcoma samples (including 40 incident prospective cases), where histologic examination was considered insufficient for clinical diagnosis. The NanoString assay had a 93% technical success rate, and an accuracy of 97.8% versus an MDM2 amplification FISH gold standard. NanoString had a considerably faster turnaround time and was cheaper than FISH.

[Analysis of 2 cases of dyspnea happening after tracheotomy and the clinical application of Mimics 10.01].

Post-intubation tracheal stenosis was a late time complication after tracheotomy but the happening of dyspnea was unusual. Diagnosing tracheal stenosis after incubation, and figuring out the location and causes of the stenosis were important. Treatment of post-incubation tracheal stenosis relied on accurate diagnosis of the type of tracheal stenosis. Computed tomography (CT) and laryngoscope could be used for detecting the stenosis but not enough. Two patients who were already under the urgent tracheotomy over 1 year were reported. However apnea was found on these two patients for a long time after traheotomy. Obviously laryngeal obstruction appeared. CT virtual bronchoscope and laryngoscope examination showed that the cannula was obstructed and plenty of granulation tissue blocked the orificium. But the exact location of the cannula and the adjacent relationship of the tissue around the cannula was equivocal. Mimics 10.01 software was used to analyze the data of the CT scan and found that a pseudo cavity was formed by granulation tissue which partly blocked the cannula in 1 case; granulation tissue occupation and scar formation in the trachea were the reason of tracheal stenosis but not the collapse of the cartilage in case 2. The purpose of this report is to discuss the cause of dyspnea after emergency tracheotomy, its diagnostic method and their management. CT virtual bronchoscope and laryngoscope should be used as a regular examination after tracheotomy to clarify the location of cannula and avoid the failure of airway opening caused by the dislocation of cannula and the complication. Trachea tissue should be protected properly during and after the tracheotomy which might decline the rate of the tissue remodeling, tracheal stenosis and dyspnea after surgery. The clinical use of Mimics 10.01 made it possible to observe morphology more directly by invasive examination and provided a significant clue to make the operation plan so that it should be used widely. Meanwhile, the method to put the cannula into its right way under the guidance of rigid endoscope and the excision of granulation tissue by semiconductor laser should become one of the best treatments of this disease. Following the method above, laryngeal obstruction was relieved after the surgery. Postoperative follow-up lasted for 1 year and recurrence was not found.

Which product characteristics are preferred by Chinese consumers when choosing pork? A conjoint analysis on perceived quality of selected pork attributes.

Due to the economic growth achieved by China over the past 20 years, Chinese consumers have changed their purchasing behavior regarding meat. Instead of buying locally produced pork, they are increasingly willing to purchase imported pork. A conjoint analysis investigated how intrinsic pork attributes (fat content and processing) and extrinsic pork attributes (origin, price, and packaging) relate to the perceived quality of pork and the choices made by Chinese consumers. A questionnaire distributed among a sample of Chinese consumers (n = 81) revealed that processing (fresh/frozen) is the most important determinant of pork choice (36%), followed by fat content (27%), origin (18%), price (12%), and packaging (6.6%). Estimates of utility showed that Chinese consumers value fresh pork highly (0.147), followed by lean pork (0.111) and pork imported from countries other than China (0.073). The findings indicate that Chinese consumer's value both intrinsic and extrinsic attributes, and these results may help the meat industry improve China's competitive meat market by developing new and more products that are tailored to the needs of the consumer.

[Taste dysfunction analysis in patients with allergic rhinitis].

Objective:To investigate the taste dysfuction and its features in patients with allergic rhinitis,and to study its influence on quality of life.Method:Three hundred and five consecutive cases were enrolled. Rhino conjunctivitis Quality of Life Questionnaire, visual analogue scale and Lund-Kennedy nasal endoscopy scores were used to assess the taste dysfunction. In addition, taste test with paper strips was used to evaluate the four basic tastes of the twenty patients with severity dysfuction VAS.Result:Taste dysfuction accounted for 18.03% (55/305) in all allergic rhintis, while hypogeusia and hypergeusia were 98.18% (54/55), 1.82% (1/55) respectively. There were significant differences of RQLQ scores in taste dysfuction group compared to no taste dysfunction group, there were positive correlated relationship, but no difference between taste function and nasal VAS scores nor Lund and Kennedy nasal endoscopy scores. Saline taste, bitter taste, sweet taste and sour taste were impaired in AR, thus, saline taste was more diminishes than another three (P< 0.05). Conclusion:Taste dysfunction is common symptom in allergic rhinitis, mainly including hypogeusia, especially saline taste.Taste dysfunction can impact patients'quality of life.

Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor.

AIMS: Recent evidence indicates that weakly positive immunohistochemical staining of oestrogen receptor (ER) is not associated reliably with a luminal subtype, with the majority reclassified as basal-like by gene expression profile. In this study we assessed the capacity of recently identified immunohistochemical markers of basal-like subtype not dependent upon ER status - positive expression of nestin or loss of inositol polyphosphate-4-phosphatase (INPP4b) - to discriminate intrinsic subtypes, focusing on clinically problematic cases with weak ER positivity. METHODS AND RESULTS: Formalin-fixed paraffin-embedded blocks, enriched for large proportions of ER-negative and ER weakly positive breast cancers, were selected from two previous studies conducted in the period 2008-13 and used for (i) RNA extraction for 50-gene subtype predictor (PAM50) intrinsic subtyping and (ii) tissue microarray construction for immunohistochemical assessment of nestin and INPP4b. Fifty-eight cases were weakly positive for ER (Allred 3-5), among which 28 (48%) were assigned as basal-like by PAM50 gene expression. In these 58 cases, the nestin/INPP4b panel identified 23 basal-like cases with a positive predictive value of 87% [95% confidence interval (CI) 78-95%] and excluded luminal subtype with a negative predictive value of 95% (95% CI 88-100%). Weakly positive ER patients assigned as basal-like by nestin/INPP4b definition demonstrated a median survival time of 45.8 months, significantly lower than 65 months among other ER weakly positive cases (P = 0.012). CONCLUSIONS: Immunohistochemical assessment of nestin and INPP4b provides an accurate, accessible and inexpensive tool to identify basal-like breast cancer subtype in the clinically problematic setting of weak ER positivity. This panel identifies poor prognosis patients who might need strong considerations for non-endocrine-based therapies.

[Investigation on the expression of microvessel pericyte coverage index and lymph vessel density in nasal polyps].

Objective: To investigate the role of lymph vessel density (LVD) and microvessel pericyte coverage index (MPI) in the pathogenesis of nasal polyps. Methods: Using immunohistochemistry and immunofluorescence double staining method, the expressions of albumin, D2-40 and CD34-α-SMA in 11 specimens of normal nasal mucosa, 26 specimens of nasal polyp and 26 specimens of inferior turbinate tissue from patients with nasal polyps were investigated. The counts of microvessel density (MVD), lymph vessel density (LVD) and microvessel pericyte coverage index (MPI) were compared. SPSS 17.0 software was used to analyze the data. Results: The nasal polyp group(0.269±0.096) had more albumin than inferior turbinate tissue group(0.159±0.078) and normal nasal mucosa group(0.138±0.045), the differences were significant (q value was 4.873, 4.446, both P<0.05). The counts of MVD in nasal polyp group (30.52±4.42) were not significantly higher than those in inferior turbinate tissue group (30.33±6.03) and normal nasal mucosa group(28.21±6.84), the differences were not significant (q value was 0.130, 1.147, both P>0.05). The MPI in nasal polyp group (0.291±0.096) was significantly lower than those in inferior turbinate tissue group(0.432±0.101) and normal nasal mucosa group(0.416±0.071), the difference was significant (q value was 5.399, 3.680, both P<0.05). The counts of LVD in the nasal polyp group(0.245±0.073) were significantly lower than those in inferior turbinate tissue group (0.431±0.054) and normal nasal mucosa group(0.470±0.078), the difference was significant (q value was 10.004, 9.328, both P<0.05). MPI expression in the nasal polyp group was negetively correlated to albumin expression(r=-0.889, P<0.05). The LVD expression in the nasal polyp group was negetively correlated to albumin expression(r=-0.901, P<0.05). Conclusion: Different LVD and MIP in nasal polyp tissues and normal nasal mucosa tissues imply that microcirculatory dysfunction plays a crucial role in the pathogenesis of nasal polyps.

Residues of carbosulfan and its metabolites carbofuran and 3-hydroxy carbofuran in rice field ecosystem in China.

The fate of carbosulfan (seed treatment dry powder) was studied in rice field ecosystem, and a simple and reliable analytical method was developed for determination of carbosulfan, carbofuran, and 3-hydroxyl carbofuran in brown rice, rice straw, paddy water, and soil. The target compounds were extracted using acetonitrile or dichloromethane, cleaned up on acidic alumina or florisil solid phase extraction (SPE) cartridge, and analyzed by gas chromatography. The average recoveries of carbosulfan, carbofuran and 3-hydroxy carbofuran in brown rice, rice straw, paddy water, and soil ranged from 72.71% to 105.07%, with relative standard deviations of 2.00-8.80%. The limits of quantitation (LOQs) of carbosulfan, carbofuran and 3-hydroxy carbofuran in the samples (brown rice, rice straw, paddy water and soil) were 0.011, 0.0091, 0.014, 0.010 mg kg(-1), 0.016, 0.019, 0.025, 0.013 mg kg(-1), and 0.031, 0.039, 0.035, 0.036 mg kg(-1), respectively. The trials results showed that the half-lives of carbosulfan, carbofuran and 3-hydroxy carbofuran in rice straw were 4.0, 2.6 days, 3.9, 6.0 days, and 5.8, 7.0 days in Zhejiang and Hunan, respectively. Carbosulfan, carbofuran and 3-hydroxy carbofuran were detected in soils. Carbosulfan and 3-hydroxy carbofuran were almost undetectable in paddy water. Carbofuran was detected in paddy water. The final residues of carbosulfan, carbofuran and 3-hydroxy carbofuran in brown rice were lower than 0.05 mg kg(-1), which were lower than 0.5 mg kg(-1) (MRL of carbosulfan) or 0.1 mg kg(-1) (MRL of carbofuran). Therefore, a dosage of 420 g active ingredient per 100 kg seed was recommended, which could be considered as safe to human beings and animals. These would contribute to provide the scientific basis of using this insecticide.

[New therapeutic strategies in allergic rhinitis].

Allergic rhinitis (AR) is a nasal inflammatory, IgE-mediated disease that occurs when some individuals inhales something he or she is allergic to, such as pollen or animal dander. It is also a refractory disease with high prevalence in the field of rhinology. The treatment of AR is really a difficult and challenging task because of the high prevalence, economic burden and the interference to the quality of life. At present, nasal corticosteroid and antihistamines were the mainly therapies, however, there is up to 40% patients not satisfactory to these therapies. So exploring new therapy or target is necessary. This article will review the results of previous studies focused on the new therapies of AR.

[Microenvironment of middle meatus involved in pathogenesis of nasal polyps-the possibility and research progress].

Chronic rhinosinusitis with nasal polyps(CRSwNP) is a complicated inflammatory disease, with increasing incidence and high recurrence rate,which the pathogenesis remains unclear. This article reviewed research progress about the relationships between middle meatus microenvironments and pathologic process of CRSwNP: including hypoxia ,microbiome imbalance, innate function of the airway epithelial barrier dysfunction. Pointing out a new direction to figure out pathogenesis of CRSwNP.

Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802).

BACKGROUND: The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented. PATIENTS AND METHODS: Of 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to-treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments. RESULTS: Median OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83-1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms. CONCLUSION: The significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients. CLINICALTRIALSGOV IDENTIFIER: NCT00874419.

Association between CC motif chemokine ligand 5 (CCL5) polymorphisms and asthma risk: an updated meta-analysis.

BACKGROUND: Findings regarding the associations between the CC motif chemokine ligand 5 (CCL5) -403G/A and -28C/G polymorphisms and asthma risk are controversial.We performed a meta-analysis to determine whether CCL5 polymorphisms are associated with asthma risk. METHODS: We searched the Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies published before June 2013. The strength of associations was calculated using ORs with 95% CIs. RESULTS: Twenty case-control studies were included in this meta-analysis. We did not observe a significant association between the CCL5 -403G/A polymorphism and asthma risk (OR, 1.10; 95% CI, 0.93-1.30; P = .25). The CCL5 - 28C/G polymorphism, however, was associated with a significantly elevated asthma risk (OR, 1.17; 95% CI, 1.02-1.33; P = .02). Subgroup analyses found that the CCL5 -28C/G polymorphism was significantly associated with asthma risk in Asians (OR, 1.16; 95% CI, 1.01-1.33; P = .04) and children (OR, 1.29; 95% CI, 1.03-1.63; P = .03). CONCLUSIONS: This meta-analysis suggests that the CCL5 -28C/G polymorphism is a risk factor for asthma.

Association between CC motif chemokine ligand 5 (CCL5) polymorphisms and asthma risk: an updated meta-analysis

Background: Findings regarding the associations between the CC motif chemokine ligand 5 (CCL5) -403G/A and -28C/G polymorphisms and asthma risk are controversial. We performed a meta-analysis to determine whether CCL5 polymorphisms are associated with asthma risk. Methods: We searched the Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies published before June 2013. The strength of associations was calculated using ORs with 95% CIs. Results: Twenty case-control studies were included in this meta-analysis. We did not observe a significant association between the CCL5 -403G/A polymorphism and asthma risk (OR, 1.10; 95% CI, 0.93-1.30; P=.25). The CCL5 -28C/G polymorphism, however, was associated with a significantly elevated asthma risk (OR, 1.17; 95% CI, 1.02-1.33; P=.02). Subgroup analyses found that the CCL5 -28C/G polymorphism was significantly associated with asthma risk in Asians (OR, 1.16; 95% CI, 1.01-1.33; P=.04) and children (OR, 1.29; 95% CI, 1.03-1.63; P=.03). Conclusions: This meta-analysis suggests that the CCL5 -28C/G polymorphism is a risk factor for asthma (AU)

Introducción: Existen discrepancias entre la asociación del riesgo de padecer asma y diferentes polimorfismos del ligando de la quimiocina CC5 (CCL5). En este trabajo se ha realizado un meta-análisis para determinar si los polimorfismos CCL5-403G / A y CCL5-28C / G se asocian con el riesgo de asma bronquial. Métodos: Se utilizaron diversas bases de datos para realizar las búsquedas de estudios publicados antes de junio de 2013, incluyendo: PubMed, EMBASE, CNKI (Infraestructura del Conocimiento Nacional Chino) y Wanfang Se calcularon los odd ratios combinados (OR) con intervalos de confianza del 95% (IC). Resultados: Se incluyeron un total de 20 estudios de casos y controles. No se encontró una asociación significativa entre el polimorfismo CCL5-403G / A y el riesgo de asma (OR = 1,10, IC del 95%: 0,93 a 1,30, p = 0,25). Por el contrario, el polimorfismo CCL5-28C / G, se asoció con un riesgo significativamente elevado de asma (OR = 1,17, IC del 95%: 1,02 a 1,33, p = 0,02). En los análisis de subgrupos, el riesgo de asma fue significativamente mayor en los asiáticos con el polimorfismo CCL5-28C / G (OR = 1.16, 95% IC 1,01-1,33, P = 0,04) y los niños (OR = 1.29, 95% IC 1,03-1,63, P = 0,03). Conclusiones: Este meta-análisis sugiere que el polimorfismo CCL5-28C / G es un factor de riesgo significativo para padecer asma bronquial (AU)

Interferon-gamma +874A/T polymorphism is associated with asthma risk: a meta-analysis.

BACKGROUND: Results regarding the association between the interferon-y (lFN-y) +874A/T polymorphism and asthma risk are controversial and ambiguous. The aim of this study was to determine with greater precision the relationship between the IFN-gamma+874A/T polymorphism and asthma using a meta-analysis. METHODS: Published literature was retrieved from 5 databases (PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure [CNKI] and Weipu). ORs with 95% Cls were used to assess the strength of association. RESULTS: Ten case-control studies involving 697 cases and 1049 controls were identified. In the overall analysis, a significant association between the +874A/T polymorphism and asthma susceptibility was found for AA vs AT + TT (OR, 1.89; 95% CI, 1.37-2.62; P=.0001). In the subgroup analysis by ethnicity, significant associations were found among whites (OR, 1.42; 95% CI, 1.04-1.93; P=.03) and Asians (OR, 2.52; 95% CI, 1.49-4.25; P=.0006). The sensitivity analysis and cumulative meta-analysis further strengthened the validity of this association. No publication bias was observed in this study. CONCLUSION: The results of this meta-analysis suggest that the IFN-gamma +874A/T polymorphism is a risk factor for asthma.

Effects of TNF-α polymorphisms on asthma risk: a systematic review and meta-analysis

Background: Several studies have examined associations between TNF-α polymorphisms and asthma risk, but the results have been conflicting. Methods: A search was performed of the PubMed, EMBASE, and Wanfang databases. Data were extracted and pooled ORs with 95% CIs were calculated. Results: Fifty-four studies were included. A significant association between the TNFA -308A/G polymorphism and asthma susceptibility was observed for AA+AG vs GG (OR, 1.39; 95% CI, 1.23-1.58; P<.001). This polymorphism was also significantly associated with asthma risk in whites (OR, 1.47; 95% CI, 1.25-1.73; P<.001), atopic asthma risk (OR, 1.38; 95% CI, 1.16-1.65; P<.001), pediatric asthma risk (OR, 1.48; 95% CI, 1.23-1.79; P<.001), and adult asthma risk (OR, 1.35; 95% CI, 1.21-1.52; P<.001). There was also a significant association between the TNFA -857C/T polymorphism and asthma risk in the recessive model (OR, 1.25; 95% CI, 1.10-1.43; P<.001). In the subgroup analyses, asthma risk was significantly increased in Asians (OR, 1.23; 95% CI, 1.07-1.41; P=.004) and atopic individuals (OR, 1.33; 95% CI, 1.13-1.57; P<.001). No significant association was found for the TNFA -238A/G polymorphism. There were insufficient data to evaluate the associations between TNFA -1031T/C and -863C/A polymorphisms and asthma risk. Conclusions: This meta-analysis suggests that TNFA -308A/G and -857C/T polymorphisms are risk factors for asthma (AU)

Antecedentes: Son varios los estudios que han examinado las asociaciones existentes entre diferentes polimorfismos del factor de necrosis tumoral alfa (TNF-α) con el riesgo de padecer asma. Sin embargo, los resultados han sido contradictorios. Métodos: Se utilizaron diversas bases de datos para realizar las búsquedas, incluyendo: PubMed, EMBASE y Wanfang. Se calcularon los odd ratios combinados (OR) con intervalos de confianza del 95% (IC). Resultados: Se incluyeron cincuenta y cuatro estudios. Se encontró una asociación significativa entre el polimorfismo TNFA-308A/G y la susceptibilidad de asma para AA+AG vs GG (OR = 1,39, IC del 95% 1,23-1,58, P <0,00001). Este polimorfismo también se asoció significativamente con el riesgo de asma en los pacientes caucásicos (OR = 1,47, IC del 95%: 1,25 a 1,73, P <0,00001), el riesgo de asma atópica (OR = 1,38, IC del 95%: 1,16 a 1,65, P = 0,0003), el riesgo de asma infantil (OR = 1,48, IC del 95%: 1,23 a 1,79, P <0,0001), y el riesgo de asma en adultos (OR = 1,35, IC del 95%: 1,21 a 1,52, P <0,00001), respectivamente. También hubo una asociación significativa entre el polimorfismo TNFA-857C/T y el riesgo de asma en el modelo recesivo (OR = 1,25, IC del 95%: 1,10 a 1,43, P = 0,0009). En los análisis de subgrupos, el riesgo de asma fue significativamente mayor en los asiáticos (OR = 1,23, IC del 95%: 1,07 a 1,41, P = 0,004) y en los individuos atópicos (OR = 1,33, IC del 95%: 1,13 a 1,57, P = 0,0006). No se encontró asociación significativa para el polimorfismo TNFA-238A/G. No hubo datos suficientes para evaluar asociaciones entre los polimorfismos TNFA-1031T/C y TNFA- 863C/A y el riesgo de asma. Conclusiones: Este meta-análisis sugiere que los polimorfismos TNFA-308A/G y TNFA-857C/T son factores de riesgo para el asma (AU)

Interferon-g +874A/T polymorphism is associated with asthma risk: a meta-analysis

Background: Results regarding the association between the interferon-g (IFN-g) +874A/T polymorphism and asthma risk are controversial and ambiguous. The aim of this study was to determine with greater precision the relationship between the IFN-g +874A/T polymorphism and asthma using a meta-analysis. Methods: Published literature was retrieved from 5 databases (PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure [CNKI] and Weipu). ORs with 95% CIs were used to assess the strength of association. Results: Ten case-control studies involving 697 cases and 1049 controls were identified. In the overall analysis, a significant association between the +874A/T polymorphism and asthma susceptibility was found for AA vs AT + TT (OR, 1.89; 95% CI, 1.37-2.62; P=.0001). In the subgroup analysis by ethnicity, significant associations were found among whites (OR, 1.42; 95% CI, 1.04-1.93; P=.03) and Asians (OR, 2.52; 95% CI, 1.49-4.25; P=.0006). The sensitivity analysis and cumulative meta-analysis further strengthened the validity of this association. No publication bias was observed in this study. Conclusion: The results of this meta-analysis suggest that the IFN-g +874A/T polymorphism is a risk factor for asthma (AU)

Antecedentes: Los resultados de los estudios publicados sobre la asociacion entre el polimorfismo del interferon-g (IFN-g) 874 A/T y el riesgo de asma han sido polemicos y ambiguos. El objetivo de este estudio ha sido determinar, con mayor precision, la relacion entre el polimorfismo del IFN-g 874 A/T y el asma, usando un meta-analisis. Metodos: Busqueda de la literatura publicada en Pubmed, EMBASE, Base de Datos Wanfang, Infraestructura Nacional China de Conocimiento (CNKI) y en la base de datos Weipu. Se utilizaron los odds ratios (OR) con intervalos de confianza del 95% (IC) para evaluar la fuerza de la asociacion. Resultados: Se encontraron diez estudios de casos y controles, con 697 casos y 1049 controles. En el analisis general, se hallo una asociación significativa entre el polimorfismo 874 A/T y la susceptibilidad al asma, para AA vs AT + TT (OR = 1,89, IC del 95%: 1,37 a 2,62, P = 0,0001). En el analisis de subgrupos, dependiendo de la etnia, se hallaron asociaciones significativas entre los caucasicos (OR = 1,42, IC del 95%: 1,04 a 1,93, P = 0,03) y entre los asiaticos (OR = 2,52, IC del 95%: 1,49 a 4,25, P = 0,0006). El analisis de sensibilidad y un meta-analisis acumulativo reforzaron aun mas la validez de esta asociacion. No se observaron sesgos de publicacion. Conclusion: Este meta-analisis sugiere que el polimorfismo del IFN-g 874 A/T es un factor de riesgo para el asma (AU)

Effects of TNF-α polymorphisms on asthma risk: a systematic review and meta-analysis.

BACKGROUND: Several studies have examined associations between TNF-α polymorphisms and asthma risk, but the results have been conflicting. METHODS: A search was performed of the PubMed, EMBASE, and Wanfang databases. Data were extracted and pooled ORs with 95% CIs were calculated. RESULTS: Fifty-four studies were included. A significant association between the TNFA-308A/G polymorphism and asthma susceptibility was observed for AA + AG vs GG (OR, 1.39; 95% CI, 1.23-1.58; P < .001). This polymorphism was also significantly associated with asthma risk in whites (OR, 1.47; 95% CI, 1.25-1.73; P < .001), atopic asthma risk (OR, 1.38; 95% CI, 1.16-1.65; P < .001), pediatric asthma risk (OR, 1.48; 95% CI, 1.23-1.79; P < .001), and adult asthma risk (OR, 1.35; 95% CI, 1.21-1.52; P < .001).There was also a significant association between the TNFA -857C/T polymorphism and asthma risk in the recessive model (OR, 1.25; 95% CI, 1.10-1.43; P < .001). In the subgroup analyses, asthma risk was significantly increased in Asians (OR, 1.23; 95% CI, 1.07-1.41; P = .004) and atopic individuals (OR, 1.33; 95% CI, 1.13-1.57; P < .001). No significant association was found for the TNFA-238A/G polymorphism. There were insufficient data to evaluate the associations between TNFA -1031T/C and -863C/A polymorphisms and asthma risk. CONCLUSIONS: This meta-analysis suggests that TNFA -308A/G and -857C/T polymorphisms are risk factors for asthma.