Robust positive association between serum urate and the risk of chronic obstructive pulmonary disease: hospital-based cohort and Mendelian randomisation study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and hyperuricaemia are both characterised by systemic inflammation. Preventing chronic diseases among the population with common metabolic abnormality is an effective strategy. However, the association of hyperuricaemia with the higher incidence and risk of COPD remains controversial. Therefore, replicated researches in populations with distinct characteristics or demographics are compellingly warranted. METHODS: This cohort study adopted a design of ambispective hospital-based cohort. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to minimise the effects of potential confounding factors. A Cox regression model and restricted cubic spline (RCS) model were applied further to assess the effect of serum urate on the risk of developing COPD. Finally, we conducted a two-sample Mendelian randomisation (MR) analysis to explore evidence of causal association. RESULTS: There is a higher incidence in the population with hyperuricaemia compared with the population with normal serum urate (22.29/1000 person-years vs 8.89/1000 person-years, p=0.009). This result is robust after performing PSM (p=0.013) and IPTW (p<0.001). The Cox model confirms that hyperuricaemia is associated with higher risk of developing COPD (adjusted HR=3.35 and 95% CI=1.61 to 6.96). Moreover, RCS shows that the risk of developing COPD rapidly increases with the concentration of serum urate when it is higher than the reference (420 µmol/L). Finally, in MR analysis, the inverse variance weighted method evidences that a significant causal effect of serum urate on COPD (OR=1.153, 95% CI=1.034 to 1.289) is likely to be true. The finding of MR is robust in the repeated analysis using different methods and sensitivity analysis. CONCLUSIONS: Our study provides convincing evidence suggesting a robust positive association between serum urate and the risk of developing COPD, and indicates that the population with hyperuricaemia is at high risk of COPD in the Chinese population who seek medical advice or treatment in the hospital.

A Case-Control Study of the Associations between EGLN1 Gene Polymorphisms and COPD.

BACKGROUND: Environmental and genetic factors are jointly involved in the development of chronic obstructive pulmonary disease (COPD). The EGLN1 gene is a major factor in upstream regulation of the hypoxia-inducible pathway. EGLN1 negatively regulates the hypoxia-inducible factors HIF-lα and HIF-2α by regulating the concentration of oxygen, mainly in a hypoxic environment. Hypoxia is a common physiologic condition during the progression of COPD, and several studies have identified genetic variants in EGLN1 as a key factor in the adaptation to hypoxic environments. However, it is still unclear whether there is an association between EGLN1 variants and the risk of developing COPD. METHODS: A case-control study was conducted in the Gannan Tibetan Autonomous Prefecture, Gansu Province. A total of 292 COPD patients and 297 healthy controls were enrolled to assess the association of EGLN1 single nucleotide polymorphisms (SNPs) (rs41303095 A>G, rs480902 C>T, rs12097901 C>G, rs2153364 G>A) with COPD susceptibility. RESULTS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G, and rs2153364 G>A polymorphisms were not associated with COPD susceptibility (p > 0.05). CONCLUSIONS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G and rs2153364 G>A polymorphisms were found in this study not to be associated with susceptibility to COPD in Gannan Tibetans.

Clinical research progress of novel antituberculosis drugs on multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

The role of EPAS1 polymorphisms on COPD susceptibility in southern Chinese.

Objective: COPD is the most common chronic respiratory disease with complex environmental and genetic etiologies. It was reported that EPAS1 might participate in the occurrence and development of respiratory diseases. However, the association between EPAS1 and COPD was unclear. Methods: First, a case-control study enrolling 1130 COPD patients and 1115 healthy controls in Guangzhou was conducted to clarify the association between EPAS1 polymorphisms and COPD susceptibility. Secondly, a prevalence study recruited 882 participants in Gansu to verify the effect of positive polymorphisms on lung function. Finally, the 10-year absolute risk considering environmental factors and genetic variations was calculated by the method of Gail and Bruzzi. Results: EPAS1 rs13419896 AA genotype reduced COPD risk in southern Chinese (AA vs. GG: adjusted OR = 0.689, 95% CI = 0.498-0.955; AA vs. GG/GA: adjusted OR = 0.701, 95% CI = 0.511-0.962). Further, the rs13419896 A allele was significantly associated with higher pre-FEV1/pre-FVC in both the Guangzhou and Gansu populations (P < 0.05). Smoking status, coal as fuels, education level, and rs13419896 G > A were finally retained to develop a relative risk model for males. Smoking status, biomass as fuels, and rs13419896 G > A were retained in the female model. The population-attributable risk of the male or female model was 0.457 (0.283-0.632) and 0.421 (0.227-0.616), respectively. Conclusions: This study first revealed that EPAS1 rs13419896 G > A decreased COPD susceptibility and could be a genetic marker to predict the 10-year absolute risk for COPD.

EPO rs1617640 A>C is a Protective Factor for Chronic Obstructive Pulmonary Disease: A Case Control Study.

BACKGROUND: The occurrence and development of chronic obstructive pulmonary disease (COPD) are regulated by environmental and genetic factors. In hypoxia, Erythropoietin (EPO) satisfies the body's need for oxygen by promoting the production of red blood cells. Hypoxia was proven to be a common physiological condition in COPD progression and associated with many complications. Some studies have found that EPO is involved in the development of COPD. But the mechanism has not been fully proven. METHODS: We conducted a case-control study enrolled 1095 COPD patients and 1144 healthy controls in Guangdong Province to evaluate the association between EPO polymorphisms (rs1617640 A>C, rs507392 A>G, rs564449 G>T) and COPD susceptibility. 872 participants from southern Gansu Province were recruited to verify the effect of EPO polymorphisms on lung function. RESULTS: EPO rs1617640 C allele reduced COPD susceptibility in southern Chinese significantly (AC vs. AA: adjusted Odds ratio (OR) = 0.805, 95% CI = 0.669-0.969; AC+CC vs. AA: adjusted OR = 0.822, 95% CI = 0.689-0.980). However, there was no association between rs507392 A>G and rs564449 G>T polymorphisms and COPD susceptibility (p > 0.05). We further observed that the rs1617640 C allele was associated with higher FEV1 and FVC in Guangdong and Gansu populations significantly (both p < 0.05). In brief, the level of FEV1 and FVC increased with the C allele number. We modeled the relative risk for men and women, in which the population-attributable risks chances were 0.449 (0.258-0.641) and 0.262 (0.128-0.396) respectively. In this model, smoking status, coal as fuels, education level, and rs1617640 A>C were finally retained for males, while smoking status, biomass as fuels, and1617640 A>C were retained for females. In the end, using the method developed by Gail and Bruzzi, we fitted a 10-year absolute risk model for southern Chinese with different individual relative risks, which was presented as a table. CONCLUSIONS: In conclusion, this study found that EPO rs1617640 A>C polymorphism is associated with COPD susceptibility in southern Chinese, and the C allele was associated with better lung function. In addition, it could also be considered a genetic marker associated with environmental factors to predict the absolute 10-year risk of COPD in southern Chinese.

Development and validation of nomogram including high altitude as a risk factor for COPD: A cross-sectional study based on Gansu population.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common and harmful disease that requires an effective tool to early screen high-risk individuals. Gansu has unique environments and customs, leading to the different prevalence and etiology of COPD from other regions. The association between altitude and COPD once attracted epidemiologists' attention. However, the prevalence in Gansu and the role of altitude are still unclarified. Methods: In Gansu, a multistage stratified cluster sampling procedure was utilized to select a representative sample aged 40 years or older. The questionnaire and spirometry examination were implemented to collect participants' information. The diagnosis and assessment of COPD were identified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion, while post-bronchodilator FEV1/FVC < LLN was for sensitivity analysis. Furthermore, the effect of high altitude on COPD was evaluated by the logistic regression model after propensity score matching (PSM). Finally, the participants were randomly divided into training and validation sets. The training set was used to screen the relative factors and construct a nomogram which was further assessed by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) in the two sets. Results: There were 2,486 eligible participants in the final analysis, of which 1,584 lived in low altitudes and 902 lived in high altitudes. Based on the GOLD criterion, the crude and standardized prevalences in Gansu were 20.4% (18.7-22.0) and 19.7% (17.9-21.6). After PSM, the logistic regression model indicated that high altitude increased COPD risk [PSM OR: 1.516 (1.162-1.978)]. Altitude, age, sex, history of tuberculosis, coal as fuel, and smoking status were reserved for developing a nomogram that demonstrated excellent discrimination, calibration, and clinical benefit in the two sets. Conclusions: COPD has become a serious public health problem in Gansu. High altitude is a risk factor for COPD. The nomogram has satisfactory efficiency in screening high-risk individuals.

Enhanced Photocatalytic Degradation of Indoor Low Concentration Gaseous Formaldehyde by Asymmetric Silveriodate Composited with 2D or 3D Bismuth Oxybromide.

Formaldehyde is one of the most hazardous and typical indoor VOCs air pollutants. Asymmetric AgIO3 was respectively composited with 3D hierarchically structured BiOBr and 2D BiOBr nanosheets to photodegrade gas-phase formaldehyde. Ag/AgIO3 /BiOBr(CMC) demonstrated better photocatalytic performance than Ag/AgIO3 /BiOBr owning to the role of biomass solvent sodium carboxymethyl cellulose in increasing the specific surface area, reducing the band gap and changing the dominant facets. Moreover, Ag nanoparticles coming from the reduction in AgIO3 were confirmed by XRD, SEM and XPS. The surface plasma resonance effect of Ag NPs improved the efficiency of the light quantum. Besides, different exposed facets of {010} in BiOBr(CMC) and {001} in BiOBr resulted in distinct oxygen vacancy structures. O 2 2 - could be generated via a two-electron transfer pathway on the {010} dominant facets surface in AABR-CMC, leading to the change in photolysis pathway and facilitating more · OH produced by AABR-CMC. Compared with pure AgIO3 and BiOBr or BiOBr(CMC), the photocatalytic efficiency of the composites was improved significantly. Optimal photodegradation efficiency for HCHO was achieved for AABR-75 and AABR-CMC50.

Nomograms predict survival benefits of radical prostatectomy and chemotherapy for prostate cancer with bone metastases: A SEER-based study.

Purpose: This study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation. Methods: A total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms. Results: Eleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms. Conclusions: Nomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.

Technology-based therapy-response evaluation of axial motor symptoms under daily drug regimen of patients with Parkinson's disease.

Background: Axial disturbances are the most disabling symptoms of Parkinson's disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity. Purpose: The present research aimed to quantify the therapy-response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera. Materials and methods: We enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman's correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data. Results: All the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P < 0.001), the height of foot lift (P < 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (r s = 0.345, P = 0.022; r s = 0.382, P = 0.010; r s = 0.314, P = 0.038; r s = 0.518, P < 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (ß = 0.593, 95% CI = 0.023-1.164, P = 0.042). Conclusion: Axial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.

A summary index derived from Kinect to evaluate postural abnormalities severity in Parkinson's Disease patients.

Postural abnormalities are common disabling motor complications affecting patients with Parkinson's disease (PD). We proposed a summary index for postural abnormalities (IPA) based on Kinect depth camera and explored the clinical value of this indicator. Seventy individuals with PD and thirty age-matched healthy controls (HCs) were enrolled. All participants were tested using a Kinect-based system with IPA automatically obtained by algorithms. Significant correlations were detected between IPA and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (rs = 0.369, p = 0.002), MDS-UPDRS-III total score (rs = 0.431, p < 0.001), MDS-UPDRS-III 3.13 score (rs = 0.573, p < 0.001), MDS-UPDRS-III-bradykinesia score (rs = 0.311, p = 0.010), the 39-item Parkinson's Disease Questionnaire (PDQ-39) (rs = 0.272, p = 0.0027) and the Berg Balance Scale (BBS) score (rs = -0.350, p = 0.006). The optimal cut-off value of IPA for distinguishing PD from HCs was 12.96 with a sensitivity of 97.14%, specificity of 100.00%, area under the curve (AUC) of 0.999 (0.997-1.002, p < 0.001), and adjusted AUC of 0.998 (0.993-1.000, p < 0.001). The optimal cut-off value of IPA for distinguishing between PD with and without postural abnormalities was 20.14 with a sensitivity, specificity, AUC and adjusted AUC of 77.78%, 73.53%, 0.817 (0.720-0.914, p < 0.001), and 0.783 (0.631-0.900, p < 0.001), respectively. IPA was significantly correlated to the clinical manifestations of PD patients, and could reflect the global severity of postural abnormalities in PD with important value in distinguishing PD from HCs and distinguishing PD with postural abnormalities from those without.

Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson's disease.

T lymphocytes are involved in the pathogenesis of Parkinson's disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO-) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28- CD27-), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.

High clinical diagnostic accuracy of combined salivary gland and myocardial metaiodobenzylguanidine scintigraphy in the diagnosis of Parkinson's disease.

Background: Decreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson's disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well. Purpose: To evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD). Methods: Thirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios. Results: The combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively. Conclusion: 131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

Automated and accurate assessment for postural abnormalities in patients with Parkinson's disease based on Kinect and machine learning.

BACKGROUND: Automated and accurate assessment for postural abnormalities is necessary to monitor the clinical progress of Parkinson's disease (PD). The combination of depth camera and machine learning makes this purpose possible. METHODS: Kinect was used to collect the postural images from 70 PD patients. The collected images were processed to extract three-dimensional body joints, which were then converted to two-dimensional body joints to obtain eight quantified coronal and sagittal features (F1-F8) of the trunk. The decision tree classifier was carried out over a data set established by the collected features and the corresponding doctors' MDS-UPDRS-III 3.13 (the 13th item of the third part of Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) scores. An objective function was implanted to further improve the human-machine consistency. RESULTS: The automated grading of postural abnormalities for PD patients was realized with only six selected features. The intraclass correlation coefficient (ICC) between the machine's and doctors' score was 0.940 (95%CI, 0.905-0.962), meaning the machine was highly consistent with the doctors' judgement. Besides, the decision tree classifier performed outstandingly, reaching 90.0% of accuracy, 95.7% of specificity and 89.1% of sensitivity in rating postural severity. CONCLUSIONS: We developed an intelligent evaluation system to provide accurate and automated assessment of trunk postural abnormalities in PD patients. This study demonstrates the practicability of our proposed method in the clinical scenario to help making the medical decision about PD.

Associations between LMO1 gene polymorphisms and central nervous system tumor susceptibility.

IMPORTANCE: LIM domain only 1 (LMO1) gene polymorphisms were previously found to be implicated in the risk of several cancers. No available studies were performed regarding the predisposing effect of LMO1 gene single nucleotide polymorphisms (SNPs) on central nervous system (CNS) tumor risk. OBJECTIVE: We aimed to determine whether the LMO1 gene SNPs were associated with the risk of CNS tumor by applying a case-control study with 191 cases and 248 controls in China. METHODS: The contributions of LMO1 gene SNPs to the risk of CNS tumor was evaluated by multinomial logistic regression. RESULTS: Based on the calculations of odds ratio (OR) and 95% confidence interval (CI), we failed to detect a significant relationship between each LMO1 gene SNP (rs110419 A>G, rs4758051 G>A, rs10840002 A>G, rs204938 A>G, and rs2168101 G>T) and CNS tumor risk, respectively. A negative association was also found in the combined effects on these five SNPs and CNS tumor risk. The stratification analysis further demonstrated the individuals with rs204938 AG/GG genotype confer to increased risk of CNS tumor compared with those with an AA genotype in males (OR: 1.74, 95% CI: 1.01-2.98, P = 0.046). INTERPRETATION: We concluded that LMO1 gene SNPs may not strong enough to influence the risk of CNS tumor in Chinese children. More studies are required to verify this association.

Association Between LIN28A Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Gliomas are the most prevalent brain tumors among children and adolescents. The occurrence and development of various malignant tumors is closely related with LIN28A gene, but its relationship with glioma susceptibility has not been widely discovered. In this case-control study, we conducted four single nucleotide polymorphisms (SNPs) (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) of LIN28A gene to investigate whether they increase the risk of glioma. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate their relationship. There was no significant correlation between four SNPs and glioma risk in single polymorphism and conjoint analysis. However, in stratification analysis, we found that rs3811463 TC/CC may add to the risk of glioma with clinical stage III (adjusted OR = 3.16, 95% CI = 1.15-8.70, P = .026) or stage III+IV patients (adjusted OR = 2.05, 95% CI = 1.02-4.13, P = .044). Our research suggested that four SNPs of LIN28A gene have a weak relationship with the risk of glioma in Chinese children. LIN28A rs3811463 TC/CC may increase the possibility of glioma in clinical stage III or stage III+IV patients which need larger samples and further confirmation.

Investigation of the Relationship between CMYC Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Glioma is a common central nervous system tumors in children. CMYC has a range of functions that are disrupted in various tumor cells, and may contribute to the occurrence and development of glioma. Two CMYC single nucleotide polymorphisms (rs4645943C>T and rs2070583 A>G) were genotyped in 190 cases and 248 controls from Wenzhou and Guangzhou hospitals. After adjusting for age and sex, odds ratio and 95% confidence interval values were calculated by logistic regression to evaluate the correlation between CMYC gene polymorphisms and glioma risk; no significant associations were detected. These results require future validation in a larger sample cohort.

Genetic variations in base excision repair pathway genes and risk of hepatoblastoma: a seven-center case-control study.

Hepatoblastoma is a rare childhood liver cancer without known explicit etiology. Base excision repair (BER) pathway genes have been implicated in the pathophysiology of cancer, yet the role of BER pathway gene single nucleotide polymorphisms (SNPs) on hepatoblastoma risk still awaits to be explored. This study aims to determine whether hepatoblastoma risk be modulated by polymorphisms in the BER pathway genes based on genotyped data from 313 cases and 1446 controls. We applied TaqMan assay to genotype these included samples. We comprehensively genotyped 20 SNPs across six genes of BER, and estimated odds ratio (ORs), 95% confidence intervals (CIs), and P-values of the selected SNPs' contribution to the risk of hepatoblastoma using logistic regression models. Only SNP rs293795 in the hOGG1 gene could significantly enhance hepatoblastoma risk under recessive model (adjusted OR=3.78, 95% CI=1.01-14.17, P=0.047). Stratified analysis revealed that rs159153 TC/CC genotype decreased hepatoblastoma risk in male subgroup. Moreover, rs293795 GG and 1-3 risk genotypes could increase hepatoblastoma risk in clinical stages I+II and male subgroups, respectively. False-positive report probability validated the reliability of the significant results. Our findings provide some clues of a potential risk effect of BER pathway gene hOGG1 SNPs on hepatoblastoma. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.

KRAS gene polymorphisms are associated with the risk of glioma: a two-center case-control study.

BACKGROUND: Glioma, also known as neuroglioma, is the most common primary tumors of the central nervous system. Many previous studies have reported associations between RAS gene polymorphisms and multiple tumors. However, the role of RAS gene polymorphisms on glioma risk has not been investigated. METHODS: We conducted a two-center case-control study to investigate whether the RAS gene polymorphisms predispose individuals to gliomas in 248 healthy controls and 191 glioma patients. RAS gene polymorphisms (rs12587 G>T, rs7973450 A>G, rs7312175 G>A in KRAS, rs2273267 A>T in NRAS) were genotyped by the TaqMan assay. The relationship between RAS gene functional single nucleotide polymorphisms (SNPs) and the risk of glioma was evaluated based on odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Individuals with KRAS rs7312175 GA genotype were more likely to develop glioma than those with GG genotype (adjusted OR =1.66, 95% CI: 1.05-2.64, P=0.030). However, the other three SNPs could not affect glioma risk. In stratified analysis of age, gender, subtypes, and clinical stages, rs7312175 GA carriers were more likely to develop glioma in the following subgroups: children less than 60 months, tumor derived from the astrocytic tumors, and clinical stages I. CONCLUSIONS: The study showed that polymorphism rs7312175 GA in the KRAS gene was associated with increased glioma susceptibility. Further investigation is warranted to confirm these findings and to better elucidate the involved biological pathways.

Role of FTO gene polymorphisms in Wilms tumor predisposition: A five-center case-control study.

BACKGROUND: Wilms tumor is the most frequently occurring renal malignancy in pediatrics. The FTO gene exhibits a featured genetic contribution to cancer development. Nonetheless, its single nucleotide polymorphism (SNP) contribution to Wilms tumor remains unknown. METHODS: In the present study, 402 Wilms tumor patients and 1198 healthy controls were successfully genotyped for FTO gene SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G and rs8047395 A>G) using TaqMan SNP genotyping assays. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from unconditional logistic regression, were applied to quantify the effects of FTO gene SNPs on Wilms tumor risk. RESULTS: We found that the rs8047395 A>G polymorphism was significantly correlated with an increased risk for Wilms tumor (GG versus AA/AG: adjusted OR = 1.38, 95% CI = 1.04-1.85, p = 0.027). Carriers with 1 and 1-2 risk genotypes are more susceptible of developing Wilms tumor than those without risk genotypes. Stratified analysis of rs8047395 and risk genotypes revealed more significant relationships with Wilms tumor risk in certain subgroups. Preliminary functional annotations revealed that the rs8047395 A allele increases expression levels of the FTO gene as determined by expression quantitative trait locus analysis. CONCLUSIONS: The present study provides evidence that rs8047395 may regulate FTO gene expression and thus confer susceptibility to Wilms tumor. The candidate FTO gene rs8047395 A>G polymorphism identified in this study warrants independent investigation.

Genetic variants in m6A modification core genes are associated with glioma risk in Chinese children.

Glioma is a highly heritable disease with a strong genetic component. The N6-methyladenosine (m6A) modification core genes play important roles in the context of cancer. However, the effects of polymorphisms in the m6A modification core genes on the risk of pediatric glioma remain undefined. Here, we intended to demonstrate the relationship between 24 functional single-nucleotide polymorphisms (SNPs) in eight m6A modification core genes and glioma risk. Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma while accounting for the subtypes of glioma. A total of 171 glioma cases and 228 controls from South China were genotyped using a TaqMan assay. The WTAP rs7766006, YTHDF2 rs3738067, and FTO rs9939609 variants conferred a statistically significant increased risk of glioma, respectively. YTHDC1 rs2293595, YTHDC1 rs3813832, and FTO rs8047395 were associated with a significant inverse association with risk of glioma, respectively. The significant associations were more predominant in stratification analyses of certain subgroups. Functional annotations revealed that WTAP rs7766006 and YTHDF2 rs3738067 could be potential functional variants by increasing expression of WTAP and YTHDF2 mRNA, respectively. Overall, these findings implicate variants in the m6A modification core genes as playing a role in pediatric glioma etiology.