A Potential Polymorphism in the Promoter of Let-7 is Associated With an Increased Risk of Intracranial Aneurysm: A Case-Control Study

Let-7 family plays a key role in the progression of atherosclerosis and intracranial aneurysm (IA). We hypothesized that rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family may be associated with the susceptibility of IA. We genotyped the 2 single nucleotide polymorphisms (SNPs) in 305 patients with IA and 401 healthy controls. The rs10877887 was analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay, and the rs13293512 was analyzed using a TaqMan SNP genotyping method. The relative expression of let-7 family was measured in plasma of cases and controls using real-time PCR. We found that the rs13293512CT genotype was associated with a significantly increased risk of developing IA in a heterozygote comparison (adjusted OR = 1.43, 95% CI, 1.00–2.05, P = 0.048) and dominant comparison (adjusted OR = 1.44, 95% CI, 1.02–2.03, P = 0.04). Combined analysis showed that the rs10877887TT and rs13293512CC/CT genotypes had a significantly increased risk of IA (OR = 1.67, 95% CI, 1.04–2.68, P = 0.03). Moreover, the levels of let-7a, let-7d, and let-7f were downregulated in IA patients, and patients with the rs13293512CC/CT genotypes had a lower level of let-7a than those with rs13293512TT genotype (P = 0.03). These findings indicate that the rs13293512CC/CT is a risk factor for the development of IA, possibly because of the genotypes resulting in a lower level of let-7a.     

Association between functional polymorphisms in the flanking region of miR-143/145 and risk of papillary thyroid carcinoma: A case-control study

MiR-143 and miR-145 were down-regulated in papillary thyroid carcinoma (PTC) involving in cell proliferation, apoptosis, migration, invasion, and epithelial to mesenchymal transition. In this study, we aimed to investigate the association between 2 functional polymorphisms (ie, rs4705342 and rs353292) in the flanking region of miR-143/145 and risk of PTC.A case-control study including 316 PTC patients and 347 controls was performed. The rs4705342 and rs353292 were genotyped by using the TaqMan allelic discrimination. The results were confirmed by DNA sequencing.For the rs4705342, a reduced risk of PTC was observed in heterozygous comparison, dominant genetic model and allele comparison (CC vs TT: adjusted OR = 0.37, 95% CI = 0.19–0.74, P = .003; CT/CC vs TT: adjusted OR = 0.64, 95% CI = 0.47–0.87, P = .005; C vs T: adjusted OR = 0.66, 95% CI = 0.52–0.85, P = .001, respectively). No significant difference was found in the genotypic distributions of the rs353292 between cases and controls.These findings indicate that the rs4705342 in the flanking region of miR-143/145 may be a protective factor against the occurrence of PTC. Further study is therefore required to investigate the correlation between the genotype and V-raf murine sarcoma viral oncogene homolog B1 V600E, rat sarcoma viral oncogene homolog mutations, rearranged in transformation/PTC1 and rearranged in transformation/PTC3.     

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61–0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54–0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55–0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff–Bloom–Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.     

Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case–Control Studies

Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association.Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs).Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52).The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.     

The Transforming Growth Factor-β1 (TGF-β1) Gene Polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and Susceptibility to Postmenopausal Osteoporosis: A Meta-Analysis

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-β1 gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-β1 T869C and TGF-β1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-β1 T869C and TGF-β1 T29C polymorphisms and PMOP (TGF-β1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-β1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-β1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03–1.75, P = 0.028); however, there was no significant association between TGF-β1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-β1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR = 1.37, 95% CI = 1.07–1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16–2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-β1 T869C and TGF-β1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.     

TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings.     

The Catalase C-262T Gene Polymorphism and Cancer Risk: A Systematic Review and Meta-analysis

Many studies suggest that catalase C-262T gene polymorphism is associated with cancer risk, but with inconsistent results. This study aimed to summarize the overall association between catalase C-262T polymorphism and cancer risk. Literature search was performed in PubMed, Embase, and other databases, studies regarding the association between catalase C-262T polymorphism and cancer risk were identified, and data were retrieved and analyzed by using Review Manager 5.0.24 and STATA 12.0. A total of 18 publications with 22 case–control studies, including 9777 cancer patients and 12,223 controls, met the inclusion criteria. Meta-analysis results showed significant association between catalase C-262 T polymorphism and cancer risk (TT vs CT + CC: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03–1.31, P = 0.01). Subgroup analyses stratified by cancer types suggested the catalase C-262T polymorphism was significantly associated with an increased prostate cancer risk (TT vs CT + CC: OR = 1.61, 95% CI = 1.17–2.22, P = 0.004); for subgroup analyses stratified by ethnicity, no associations between this polymorphism and Asians or whites were identified (CT + TT vs CC: OR = 1.11, 95% CI = 0.98–1.26, P = 0.09 for whites; OR = 1.19, 95% CI = 0.78–1.80, P = 0.42 for Asians). In summary, the catalase C-262T polymorphism may be a risk factor for cancer with cancer type-specific effects. Further studies should be performed to confirm these findings.     

The association between polymorphism of the long noncoding RNA,Plasmacytoma variant translocation 1, and the risk of gastric cancer

Genetic polymorphisms of plasmacytoma variant translocation 1 can affect various tumors including gastro-intestinal, sexual hormone sensitive cancers and lymphoma. Accumulated evidence have shown that plasmacytoma variant translocation 1 acts as an oncogene and tumor suppressor in various cancers. In fact, the rs13255292 and rs2608053 single nucleotide polymorphisms of plasmacytoma variant translocation 1are known to affect lymphoma; however, their effects on gastric cancer are primarily unknown. In this study, we evaluated the association between these plasmacytoma variant translocation 1 polymorphisms and the risk of gastric cancer.In the present study, 462 patients diagnosed with gastric cancer and 377 cancer-free controls were enrolled. The TaqMan genotyping assay was used to analyze the association between rs13255292 and rs2608053 single nucleotide polymorphisms and the risk of gastric cancer.The rs2608053 dominant model (CT + TT) was associated with a decreased risk of gastric cancer in T3 + T4 (odds ratio [OR] = 0.61, confidence interval (CI) = 0.41 – 0.92, P = .019), and stage III Gastric cancer subgroups (OR = 0.59, 95% CI = 0.38 – 0.91, P = .017) compared to the CC genotype. When stratified analysis by sex was carried out, the rs13255292 dominant model (CT + TT) had a significant association with an increased risk of gastric cancer in the female negative lymph node metastasis gastric cancer subgroup, compared to the CC genotype (OR = 1.96, 95% CI = 1.16 – 3.30, P = .012). The recessive model (TT) of rs13255292 was associated with an increased risk of gastric cancer in the male T3 + T4 gastric cancer subgroups compared to the CC + CT genotype (OR = 3.82, 95% CI = 1.02 – 14.33, P = .047). The dominant model (CT + TT) of rs2608053 was related to a decreased risk of gastric cancer in male T3 + T4 (OR = 0.57, 95% CI = 0.33 – 0.98, P = .042) and stage III gastric cancer subgroups (OR = 0.49, 95% CI = 0.27 – 0.89, P = .020) compared to the CC genotype.The rs13255292 and rs2608053 single nucleotide polymorphisms in plasmacytoma variant translocation 1 may contribute to susceptibility of gastric cancer. Further studies with more subjects and different ethnic groups are needed to validate our results.     

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk

Background:Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.Methods:Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).Results:Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).Conclusion:The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.     

Association Between 3 IL-10 Gene Polymorphisms and Cardiovascular Disease Risk: Systematic Review With Meta-Analysis and Trial Sequential Analysis

Previous studies have yielded controversial results related to the contribution of interleukin 10 (IL-10) gene polymorphisms (IL-10 -592C/A, IL-10 -1082G/A, and IL-10 -819C/T) in the progression of cardiovascular disease (CVD). Thus, we performed a meta-analysis to summarize this situation.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library with the last search up to July 7, 2015. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis was conducted for all significant findings. Genotype-based mRNA expression analysis was also performed using data from 270 individuals with different ethnicities.Finally, 19 studies for IL-10 -592C/A polymorphism (7284 cases and 7469 controls), 21 studies for IL-10 -1082G/A polymorphism (8263 cases and 5765 controls), and 12 studies for IL-10 -819C/T polymorphism (4502 cases and 3190 controls) were included in the meta-analyses. With respect to IL-10 -819C/T polymorphism, statistically significant decreased CVD risk was found when all studies were pooled into the meta-analysis (T vs C: OR = 0.91, 95% CI = 0.84–0.98; TT + TC vs CC: OR = 0.90, 95% CI = 0.81–1.00). Subgroup analyses stratified by disease subtype suggested the -819C/T polymorphism was significantly associated with a decreased CAD risk (T vs C: OR = 0.90, 95% CI = 0.83–0.97; TT vs CC: OR = 0.81, 95% CI = 0.66–1.00; TT vs TC + CC: OR = 0.82, 95% CI = 0.69–0.98; TT + TC vs CC: OR = 0.89, 95% CI = 0.80–0.99), which was noteworthy finding as evaluated by FPRP. However, with regard to IL-10 -592C/A and IL-10 -1082G/A polymorphisms, no significant association with CVD risk was observed in the overall and subgroup analyses.In conventional meta-analyses, the results suggested that IL-10 -819C/T polymorphism was associated with decreased risk of CVD, especially CAD outcome, whereas IL-10 -592C/A and IL-10 -1082G/A polymorphisms might have no influence on the susceptibility of CVD. However, trial sequential analysis does not allow us to draw any solid conclusion for the association between IL-10 -592C/A or IL-10 -1082G/A polymorphism and CVD risk. Further large and well-designed studies are still needed.     

Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B,Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population: A Case–Control Study

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC).A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms.Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04–2.20, P = 0.029), 1.48 (95% CI = 1.03–2.14, P = 0.035), and 1.51 (95% CI = 1.14–1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05–4.22, P = 0.035), 2.00 (95% CI, 1.01–3.95, P = 0.047), and 1.93 (95% CI = 1.14–3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16–2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23–2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05–2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52–0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases.Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.     

The Polymorphism of CYP2E1 Rsa I/Pst I Gene and Susceptibility to Respiratory System Cancer: A Systematic Review and Meta-Analysis of 34 Studies

The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers.Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association.PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case–control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer.A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20–2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23–2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74–0.91, P < 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.83, 95% CI = 0.76–0.90, P < 0.001), and allele contrast model (C2 vs C1: OR = 0.85, 95% CI = 0.73–1.00, P = 0.045). With regard to ethnicity subgroup analysis, there was significant association in Asian population in heterozygote model (C1C2 vs C1C1: OR = 0.85, 95% CI = 0.78–0.94, P = 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.88, 95% CI = 0.81–0.95, P = 0.001), and recessive model (C2C2 vs C1C2/C1C1: OR = 1.25, 95% CI = 1.01–1.53, P = 0.036).CYP2E1 Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.     

Role of Endoglin Insertion and rs1800956 Polymorphisms in Intracranial Aneurysm Susceptibility: A Meta-Analysis

Endoglin is an essential molecule during angiogenesis, vascular development, and integrity. Till now, many studies have investigated the association between endoglin polymorphisms and intracranial aneurysm (IA) risk, with the results remained inconclusive. Therefore, we performed a meta-analysis to summarize the possible association.We searched PubMed and Embase until June 2015 to identify studies addressing the association between endoglin polymorphisms and IA risk. The summary odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated to assess the strength of the association.Eleven studies with a total of 1501 cases and 2012 controls were finally included in this meta-analysis, with 10 studies investigating endoglin 6-bp insertion (6bINS) polymorphism and 4 studies investigating 1800956 polymorphism. No significant association between endoglin 6bINS polymorphism and IA risk was detected in overall estimation (I/I vs wt/I + wt/wt: OR = 1.21, 95% CI = 0.87–1.69) or in the subgroup analysis by ethnicity, control source, or ruptured status. However, we observed an association with borderline significance of 6bINS with IA occurrence (I/I vs wt/I + wt/wt: OR = 1.49, 95% CI = 0.99–2.25, P = 0.058) in studies applying matched controls. Furthermore, we detected a significant association for 6bINS polymorphism of endoglin with increased risk of familial IA (I vs wt, OR = 1.64, 95% CI = 1.10–2.42) but not sporadic IA (I vs wt, OR = 1.09, 95% CI = 0.68–1.45). With regard to rs1800956, our pooled results indicated a significantly decreased IA risk in individuals carrying C allele (C/C vs G/C + G/G: OR = 0.65; 95% CI = 0.45–0.94).This meta-analysis provided no evidence for the association between 6bINS polymorphism with overall IA risk. However, we detected a significant association of 6bINS allele with increased risk of familial IA. Also, we found that rs1800956 was significantly related to IA occurrence. Further, well-designed studies with large sample size are warranted and updated meta-analysis is needed to verify our findings.     

Association Between IL-4 Polymorphisms and Risk of Liver Disease: An Updated Meta-Analysis

Interleukin-4 (IL-4) polymorphisms have been reported to influence an individual''s susceptibility to liver disease as it is a central anti-inflammatory Th2 cytokine; however, these results remain controversial.A comprehensive meta-analysis of the relevant literature was thus performed to better estimate the relationship between IL-4 polymorphisms and liver disease.Systematic searches of various databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) for studies published before July 5, 2015 were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the association. Subgroup analyses, meta-regression, Galbraith plots, and sensitivity analyses were also performed.A total of 16 case–control studies, of which 15 involved the -590C/T polymorphism and 3 involved the -33T/C polymorphism, were included in the study. With respect to the -590C/T polymorphism, a significantly increased risk of liver diseases was found in the overall population (TT + CT vs CC: OR = 1.25, 95% CI = 1.06–1.49, P = 0.009 and CT vs CC: OR = 1.22, 95% CI = 1.00–1.48, P = 0.048) and the Asian population (TT + CT vs CC: OR = 1.28, 95% CI = 1.04–1.57, P = 0.020). Further subgroup analyses also showed significant associations between the -590C > T polymorphism and the risk of hepatitis C infection and hepatocellular carcinoma. However, no association was found between the -33T/C polymorphism and risk of liver diseases in all comparison models.This meta-analysis suggested that the IL-4 -590C > T polymorphism is associated with an increased risk of hepatitis C infection and hepatocellular carcinoma, especially among the Asian population.     

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I² index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I² = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I² = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I² = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I² = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I² = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.     

Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis

Objective:To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer.Methods:Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots.Results:Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190–1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216–1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172–1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778–0.933, P = .001).Conclusion:The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility.     

Genetic Variations in Key MicroRNAs are Associated With the Survival of Nonsmall Cell Lung Cancer

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules involved in carcinogenesis. It has been identified that genetic variations in miRNAs contribute to cancer risk, prognosis, and survival. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) of several key miRNAs (miR-184, miR-218, and miR-124) were associated with the prognosis of nonsmall cell lung cancer (NSCLC) in a clinical cohort study including 1001 cases. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs). We found that 5 SNPs were associated with NSCLC survival (rs919968, rs3775815, rs4867902, and rs6122390 in an additive model: adjusted HR = 1.15, 95% CI = 1.02–1.29; adjusted HR = 0.78, 95% CI = 0.67–0.91, adjusted HR = 1.24, 95% CI = 1.09–1.41; adjusted HR = 1.21, 95% CI = 1.07–1.36, respectively; rs298206 in a dominant model: HR = 1.25, 95% CI = 1.05–1.49). Even after the Bonferroni correction, 3 SNPs remained significant (adjusted P = 0.010, 0.010, and 0.032 for rs3775815, rs4867902, and rs6122390, respectively). Additionally, the combined analysis of these 5 SNPs showed a significant locus-dosage effect between number of unfavorable alleles (rs919968-A, rs3775815-C, rs4867902-G, rs6122390-A, and rs298206-T) and death risk of NSCLC (P for trend < 0.001). A statistically significant multiplicative interaction was found between the genotypes of rs4867902 and surgical operation status (P_int = 0.013). These findings indicated that genetic variations in miRNAs (miR-184, miR-218, and miR-124) might be prognostic markers for NSCLC patients.