Lung cancer is the most common diagnosed malignancy and the leading cause of cancer-related mortality worldwide. Murine double minute 2 (MDM2) SNP309 polymorphisms have been reported to influence the risk of lung cancer. However, the published studies together with four subsequent meta-analyses have yielded contradictory results. To examine this inconsistency, we conducted a meta-analysis of 6,696 lung cancer cases and 7,972 controls from eight published case-control studies using METAGEN. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with STATA software and used to assess the strength of the association. In the overall analysis, a significant association between MDM2 SNP309 polymorphism and lung cancer risk was observed (OR, 1.143; 95% CI, 1.047–1.247). Moreover, stratified by ethnicity, a significant association was found in Asians (OR, 1.260; 95% CI, 1.111–1.429), but not in Europeans. Subgroup analysis of gender, histology and smoking status suggested that the MDM2 SNP309 genotype was associated with increased lung cancer risk in women (OR, 1.282; 95% CI, 1.062–1.548) and never smokers (OR, 1.328; 95% CI, 1.119–1.575). No statistically significant association was observed in males and ever smoking population, and no association was found in subgroup analysis based on histology. In conclusion, the association between MDM2 SNP309 and lung cancer was statistically significant, particularly in Asians, women and never smoking population.

Summary A relationship between endometriosis and tumor necrosis factor (TNF‐α) and interleukin‐6 (IL‐6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta‐analysis to explore whether TNF‐α/IL‐6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF‐α/IL‐6 gene polymorphisms and endometriosis risk. An association of TNF‐α gene ‐1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30–0.82, I2 = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30–0.82, I2 = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29–0.83, I2 = 10.6%, P = 0.327). In addition, TNF‐α‐238A/G and IL‐6 ‐174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF‐α‐238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01–2.48). For the IL‐6 ‐174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04–2.31). No associations were detected between the TNF‐α‐308A/G and IL‐6 ‐634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF‐α gene ‐1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF‐α‐238A/G and IL‐6 ‐174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF‐α‐308A/G and IL‐6 ‐634C/G gene polymorphisms.

This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor α (TNF-α) are associated with the risk of Alzheimer’s disease (AD) and vascular dementia (VaD). Using the criteria of the NINCDS-ADRDA and NINDS-AIREN, 125 AD patients, 57 VaD patients and 109 ethnically matched nondemented controls were enrolled. The HSP70-1 –110 A/C and TNF-α –1031 T/C, –863 C/A and –857 C/T polymorphisms were analyzed by means of genotype or haplotype association methods. None of the four genotypes examined showed a statistically significant difference in genotype distribution between the AD cases and controls. However, the HSP70-1 –110 CC genotype occurred more frequently among AD cases (p = 0.0821; odds ratio: 2.08; 95% confidence interval, CI: 0.92–4.98). The overall genotype distribution among the VaD cases tended to be different at the HSP70-1 –110 and TNF-α –1031 sites (p = 0.0604 and 0.0316, respectively). The HSP70-1 –110 CC genotype was more frequent (p = 0.0459), and the association of the –110 CC genotype with VaD was evident (p = 0.0207; odds ratio: 3.22; 95% CI: 1.20–8.87). The more frequent TNF-α –1031 TC genotype (p = 0.0614) was also evidently associated with VaD (p = 0.0209; odds ratio: 2.32; 95% CI: 1.14–4.78). Multivariate analysis demonstrated the synergistic effect of the HSP70-1 –110 CC and TNF-α –1031 TC/CC genotypes on VaD (p = 0.0091; odds ratio: 10.09; 95% CI: 2.01–75.97). Haplotype analysis among TNF-α –1031, –863, –857 sites revealed that –1031C–857C may act as a risk haplotype among VaD cases (p = 0.0132, odds ratio: 2.26; 95% CI: 1.19–4.33). Our results suggest a potential protective role for HSP70 in both VaD and AD, whereas TNF-α may act as a risk factor only for VaD, and not for AD.

No abstract

Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 μg/ml to 6.25×10-5 μg/ml, among which the most profound response was observed with 6.25×10-6 μg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions.