A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo.

The prognosis and overall survival of castration-resistant prostate cancer (CRPC) patients are poor. The search for novel and efficient anti-CRPC agents is therefore extremely important. WM-3835 is a cell-permeable, potent and first-in-class HBO1 (KAT7 or MYST2) inhibitor. Here in primary human prostate cancer cells-derived from CRPC patients, WM-3835 potently inhibited cell viability, proliferation, cell cycle progression and in vitro cell migration. The HBO1 inhibitor provoked apoptosis in the prostate cancer cells. It failed to induce significant cytotoxicity and apoptosis in primary human prostate epithelial cells. shRNA-induced silencing of HBO1 resulted in robust anti-prostate cancer cell activity as well, and adding WM-3835 failed to induce further cytotoxicity in the primary prostate cancer cells. Conversely, ectopic overexpression of HBO1 further augmented primary prostate cancer cell proliferation and migration. WM-3835 inhibited H3-H4 acetylation and downregulated several pro-cancerous genes (CCR2, MYLK, VEGFR2, and OCIAD2) in primary CRPC cells. Importantly, HBO1 mRNA and protein levels are significantly elevated in CRPC tissues and cells. In vivo, daily intraperitoneal injection of WM-3835 potently inhibited pPC-1 xenograft growth in nude mice, and no apparent toxicities detected. Moreover, intratumoral injection of HBO1 shRNA adeno-associated virus (AAV) suppressed the growth of primary prostate cancer xenografts in nude mice. H3-H4 histone acetylation and HBO1-dependent genes (CCR2, MYLK, VEGFR2, and OCIAD2) were remarkably decreased in WM-3835-treated or HBO1-silenced xenograft tissues. Together, targeting HBO1 by WM-3835 robustly inhibits CRPC cell growth.

Long Non-coding RNAs LINC01679 as a Competitive Endogenous RNAs Inhibits the Development and Progression of Prostate Cancer via Regulating the miR-3150a-3p/SLC17A9 Axis.

Long non-coding RNAs (lncRNAs) have been indicated as the candidate factors to predict cancer prognosis. However, it is still unknown whether lncRNA combinations may be utilized for predicting overall survival (OS) of prostate cancer (PCa). The present work focused on selecting the potent OS-related lncRNA signature for PCa and studying its molecular mechanism to enhance the prognosis prediction accuracy. Differentially expressed lncRNAs (DElncRNAs) or differentially expressed genes (DEGs) were obtained based on TCGA database by R software "edgeR" package. lncRNAs or mRNAs significantly related to PCa were screened through univariate as well as multivariate Cox regression, for the construction of the risk model for prognosis prediction. Moreover, this constructed risk model was validated through ROC analysis, univariate regression, and Kaplan-Meier (KM) analysis. Additionally, we built a lncRNA-miRNA-mRNA ceRNA network through bioinformatics analysis. Colony formation, CCK-8, flow cytometry, scratch, and Transwell assays were performed based on PCa cells subjected to small interfering RNA (siRNA) targeting LINC01679/SLC17A9 and vector expressing LINC01679/SLC17A9 transfection. Thereafter, the ceRNA mechanism was clarified via qRT-PCR, Western blotting (WB), RNA pull-down, and luciferase reporter assays. Nude mouse tumor xenograft was established to examine LINC01679's oncogenicity within PCa cells. According to our results, LINC01679 depletion promoted cell proliferation, metastasis, tumor growth, and inhibited cell apoptosis in vivo and in vitro, which was also associated with poor survival. LINC01679 regulated miR-3150a-3p level by sponging it. Importantly, miR-3150a-3p overexpression was related to the increased proliferation and decreased apoptosis of PCa cells. Rescue assays suggested that miR-3150a-3p mimics rescued the repression on PCa progression mediated by LINC01679 upregulation, but SLC17A9 downregulation reversed the miR-3150a-3p inhibitor-mediated repression on PC progression. Importantly, SLC17A9 downregulation rescued the repression on PCa progression mediated by LINC01679 upregulation. LINC01679 and SLC17A9 are tightly associated with certain clinicopathological characteristics of PCa and its prognostic outcome. In addition, LINC01679 is the ceRNA that suppresses PCa development through modulating the miR-3150a-3p/SLC17A9 axis.

Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases.

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvß3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

New findings in the roles of Cyclin-dependent Kinase inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 G/C and rs4977574 A/G variants on the risk to coronary heart disease.

The relationship between Cyclin-Dependent Kinase Inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) variants rs1333049 G/C and rs4977574 A/G and the risk of coronary heart disease is unclear. We conducted an update analysis incorporating odds ratios and 95% confidence intervals to assess the correlation. Furthermore, we used in silico analysis to investigate the genes and proteins that interact with CDKN2B. Fifty case-control studies with a sample size of 35,915 cases and 48,873 controls were involved. We revealed that the rs1333049 C allele could increase the risk of coronary heart disease in the overall analysis (allele comparison, OR = 1.13, 95%CI = 1.05-1.21, P = 0.001; homozygous contrast, OR = 1.29, 95%CI = 1.11-1.49, P = 0.001; dominant comparison, OR = 1.14, 95%CI = 1.03-1.27, P = 0.011; recessive comparison, OR = 1.21, 95%CI = 1.10-1.34, P < 0.001). In subgroup analysis, positive correlations were detected in studies involving West and East Asians and in population-based control studies. The rs4977574 G allele was also a risk factor for coronary heart disease (allelic comparison, P = 0.001; heterozygous comparison, P = 0.003; homozygous comparison, P < 0.001; dominant comparison, P = 0.001). These results indicate correlation of CDKN2B-AS1 rs1333049 G/C and rs4977574 A/G variants may be correlated with the risk of coronary heart disease. Abbreviations CDK: Cyclin Dependent Kinase; CCND: G1/S-specific cyclin-D; CDKN: Cyclin Dependent Kinase Inhibitor; GWAS: Genome-wide association study; CDKN2B-AS1: Cyclin-Dependent Kinase Inhibitors 2B Antisense RNA 1; CHD: Coronary heart disease; MAF: minor allele frequencies; HWE: Hardy-Weinberg equilibrium of controls; CI: confidence interval; COL8A2: Collagen type VIII alpha 2 chain; HB: Hospital-based; ORs: odds ratios; ITGA11: Integrin subunit alpha 11; LTBP: Latent transforming factor beta binding protein; PB: Population-based; IBC: Itmat Broad Care; NA: Not applicable; PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism; MI: Myocardial Infarction; SNP: single nucleotide polymorphism; SMAD: Mothers against decapentaplegic homolog; RT-PCR: Real-time polymerase chain reaction; UK: United Kingdom.

Update analysis on the association between Methionine synthase rs1805087 A/G variant and risk of prostate cancer.

Previous studies have investigated the association of the rs1805087 A/G variant of Methionine synthase gene with the susceptibility to prostate cancer (PCa). Nevertheless, the conclusions remain divergent. We performed a systemic analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs) to assess Methionine synthase rs1805087 A/G variant and PCa risk. Furthermore, we utilized in silico analysis to investigate the relationship between Methionine synthase expression and the overall survival (OS) time. Totally, 10,666 PCa patients and 40,750 controls were included. We observed that Methionine synthase rs1805087 A/G variant is associated with an elevated risk of PCa (G-allele vs. A-allele: OR = 1.06, 95% CI = 1.01-1.11, P = 0.013; heterozygous model: OR = 1.08, 95% CI = 1.02-1.14, P = 0.009; dominant model: OR = 1.08, 95% CI = 1.02-1.14, P = 0.007). During stratified analysis, similar results were obtained in Asian populations, hospital-based, high quality studies and that with large sample size. Moreover, in silico analysis indicated the Methionine synthase expression is down-regulated in both young and old PCa subjects (P < 0.05). Compared with the normal subjects, the down-regulated expression of Methionine synthase was found in PCa cases with Gleason score 6 to 9. Our study showed that Methionine synthase rs1805087 A/G variant may be associated with susceptibility of PCa, especially in Asian populations, hospital-based studies and that with high quality and large sample size. Furthermore, Methionine synthase rs1805087 A/G variant may be related to the prognosis of PCa.

Association of C-reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer.

The correlation between rs1205, rs2808630 variants of C-reactive protein (CRP) gene and susceptibility of cancer has been assessed previously, but with conflicting results. We adopted odds ratios (ORs) with 95% confidence intervals (CIs), in silico tools and enzyme-linked immunosorbent assay (ELISA) analysis to evaluate this association. Totally, 10,614 cancer subjects and 33,294 controls were involved in the pooled analysis. When all the studies were pooled, no significant correlation was indicated between the two variants and cancer risk. However, in stratification analysis by ethnicity, we found that CRP rs1205 C>T polymorphism was associated with an elevated risk of cancer in Asians (T-allele vs. C-allele, OR = 1.20, 95% CI = 1.06-1.36, pheterogeneity = .226; TT vs. CC, OR = 1.48, 95% CI = 1.14-1.93, pheterogeneity = .089). Similar findings were observed for rs2808630 variant. In silico tools showed that lung adenocarcinoma participants with high CRP expression may have shorter overall survival time than low expression group. ELISA analysis indicated that CRP expression in prostate adenocarcinoma subjects with TT + TC genotypes was statistically higher than in those with CC genotypes. CRP rs1205 C>T and rs2808630 T>C polymorphism may be associated with cancer risk, especially for Asians.

Association between SOD2 V16A variant and urological cancer risk.

BACKGROUND: The correlation between superoxide dismutase 2 (SOD2) V16A variant and urological cancer susceptibility has been widely studied, however, with divergent results. RESULTS: Totally, 9,910 cancer patients and 11,239 control subjects were enrolled. V16A variant is associated with an increased susceptibility to urological cancer (A-allele vs. V-allele: OR = 1.06, 95% CI = 1.00 - 1.13, P = 0.047; AA+AV vs. VV: OR = 1.09, 95% CI = 1.02 - 1.16, P = 0.008), especially for prostate cancer (PCa). Serum SOD2 level of PCa patients with VV+VA genotypes was lower than in those with AA genotypes. SOD2 expression is downregulated in both prostate and bladder cancer, as compared to the control. Furthermore, SOD2 was found to be downregulated in more advanced PCa participants, as compared to the ones in early stages. PCa subjects with low SOD2 expression displayed a shorter disease-free survival (DFS) time compared to that of the high SOD2 expression counterparts. CONCLUSIONS: The SOD2 V16A variant may be associated with increased urological cancer susceptibility, especially for prostate cancer. METHODS: A pooled analysis utilizing odds ratios (ORs), in silico tools and ELISA was adopted to demonstrate this association. We also used immunohistochemical staining (IHS) to assess SOD2 expression.

MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not related to risk of cancer.

BACKGROUND: Several studies have focused on the relationship between MMP-8 variants and cancer risk, but they have been unsuccessful in drawing reliable conclusions. METHODS: We employed odds ratio (OR) together with 95% confidence interval (CI) to assess the correlation between MMP-8 C-799 T, Lys460Thr, and Lys87Glu polymorphisms and cancer risk. We further employed in silico tools to evaluate the effect of MMP-8 expression on cancer susceptibility and overall survival time. RESULTS: A total of 8140 patients with malignant carcinoma and 10,529 healthy individuals (control) were enrolled. Overall, the analysis showed that the relationship between three MMP-8 variants and cancer susceptibility was not significant (allelic contrast, C-799 T: OR = 0.98, 95% CI = 0.92-1.04, Pheterogeneity = 0.068; Lys460Thr: OR = 0.94, 95% CI = 0.67-1.32, Pheterogeneity = 0.905; Lys87Glu: OR = 1.05, 95% CI = 0.93-1.18, Pheterogeneity = 0.968). Similar results were observed in subgroup analysis by ethnicity, cancer type, and source of control. In silico analysis indicated that MMP-8 expression was elevated in bladder cancer tissue compared to that in the control. However, both the higher and lower MMP-8 expression groups did not show an impact on the overall survival time of the patients. CONCLUSIONS: MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not participant with the susceptibility of cancer.

The association between three AXIN2 variants and cancer risk.

Plenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme-linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63-0.92; Pheterogeneity = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35-0.84; Pheterogeneity = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population-based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population-based studies. Future large scale and well-designed research are required to validate these effects in more detail.

VEGF gene rs3025039C/T and rs833052C/A variants are associated with bladder cancer risk in Asian descendants.

INTRODUCTION: Polymorphisms of vascular endothelial growth factor (VEGF) gene were evaluated in a number of studies to evaluate bladder cancer (BCa) susceptibility but with controversial conclusions. MATERIAL AND METHODS: We performed a pooled analysis and used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to investigate the correlation between VEGF gene rs3025039C/T and rs833052C/A variants and risk of BCa. Furthermore, we utilized in silico tools to demonstrate the relationship of VEGF expression correlated with BCa susceptibility and survival time. RESULTS: A total of eight studies including 4359 BCa patients and 5417 control subjects were enrolled in our study. For VEGF rs3025039C/T, a significant association was indicated between this variant and BCa risk in homozygote comparison (OR = 1.51; 95% CI = 1.13-2.02; P heterogeneity = 0.815) and recessive genetic model (OR = 1.49; 95% CI = 1.12-1.99; P heterogeneity = 0.874), in particular in an Asian population subgroup. For VEGF rs833052C/A, we observed a positive association between this variant and BCa susceptibility in Asian descendants. Results from in silico tool showed evidence that VEGF expression in bladder carcinoma tissue is higher than that in normal counterpart (transcripts per kilobase million = 7.21 vs 6.85; P < 0.05). CONCLUSIONS: The VEGF gene rs3025039C/T and rs833052C/A variants may contribute to the risk of developing BCa, especially in Asian descendants. Future larger sample studies should be continued to focus on this issue in more detail.

Association between three genetic variants in kallikrein 3 and prostate cancer risk.

BACKGROUND: Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. METHODS: Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. RESULTS: The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64-0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42-0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65-0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41-0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.

Human methionine synthase A2756G polymorphism increases susceptibility to prostate cancer.

BACKGROUND/AIMS: Previous results on the association between MTR gene A2756G polymorphism and PCa risk are inconclusive. METHODS: We used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to evaluate the correlation between MTR A2756G polymorphism and risk of PCa in meta-analysis. Serum expression of MTR was detected by ELISA and in-silico tools were utilized to assess this variant. RESULTS: Our study included 2,921 PCa patients and 3,095 control subjects. The results indicated that the MTR A2756G polymorphism is linked with an increased risk of PCa using three genetic models (G-allele vs. A-allele: OR = 1.16, 95%CI = 1.04 - 1.30; GA vs. AA: OR = 1.17, 95%CI = 1.02 - 1.33; GG+GA vs. AA: OR = 1.18, 95%CI = 1.04 - 1.34). Stratified analysis produced similar results. A significant association was also indicated in advanced PCa from the meta-analysis. Finally, our experiments showed evidence that serum MTR levels in PCa patients with AA genotypes were statistically higher than in those with GG/GA genotypes. CONCLUSIONS: Our present study suggests that the MTR A2756G polymorphism may contribute to the risk of developing PCa, particularly in Asian and hospital-based studies. Moreover, serum MTR might be utilized in diagnosis of PCa.

Updated analysis of vitamin D receptor gene FokI polymorphism and prostate cancer susceptibility.

INTRODUCTION: Polymorphisms of the vitamin D receptor (VDR) gene have been investigated in various case-control studies to evaluate prostate cancer susceptibility; however, published data on the association between vitamin D receptor gene FokI polymorphism and prostate cancer risk are inconclusive. MATERIAL AND METHODS: To assess the impact of vitamin D receptor gene FokI polymorphism, we performed a meta-analysis of eligible studies including 9,720 patients and 9,710 control subjects. RESULTS: The overall results indicated no obvious association of this variant on prostate cancer risk. However, in subgroup analysis by ethnicity, positive associations existed in Caucasian descendents for allelic contrast (OR = 1.03, 95% CI: 1.00-1.06, pheterogeneity = 0.552, p = 0.026) and the dominant genetic model (OR = 1.03, 95% CI: 1.00-1.05, pheterogeneity = 0.856, p = 0.032). In the subgroup analysis by tumor stage, there was a significant association between this variant and advanced prostate cancer under the recessive genetic model (OR = 1.15, 95% CI: 1.01-1.32, pheterogeneity = 0.469, p = 0.032). In the subgroup analysis by source of control, association of the VDR FokI polymorphism and prostate cancer susceptibility was also found in population-based studies under homozygote comparison and the recessive genetic model. CONCLUSIONS: The VDR FokI polymorphism may contribute to the risk of developing prostate cancer in Caucasian and population-based studies. Further large, well-designed studies are warranted to confirm this conclusion in more detail.

Association of a common genetic variant in RNASEL and prostate cancer susceptibility.

The RNASEL gene (2', 5'-oligoisoadenylate synthetase-dependent) encodes a ribonuclease that plays a significant role in the apoptotic and antiviral activities of interferons. Various studies have used polymorphisms in the RNASEL gene to evaluate prostate cancer risk but studies that show an association between RNASEL Arg462Gln (1385G>A, R462Q, rs486907) polymorphism and prostate cancer risk are somewhat inconclusive. To assess the impact of RNASEL Arg462Gln polymorphism on prostate cancer risk, we conducted a meta-analysis of all available studies including 11,522 patients and 10,976 control subjects. The overall results indicated no positive association between the variant and prostate cancer risk. However, in a subgroup analysis by ethnicity, obvious associations were observed in Hispanic Caucasians for allelic contrast (OR = 1.18, 95% CI = 1.00 - 1.39, Pheterogeneity = 0.010), homozygote comparison (OR = 1.50, 95% CI = 1.02 - 2.20, Pheterogeneity = 0.001), and the recessive genetic model (OR = 1.44, 95% CI = 1.01 - 2.05, Pheterogeneity = 0.002) ; and in African descendants for homozygote comparison (OR = 2.59, 95% CI = 1.29 - 5.19, Pheterogeneity = 0.194) and the recessive genetic model (OR = 2.61, 95% CI = 1.30 - 5.23, Pheterogeneity = 0.195). In conclusion, the RNASEL Arg462Gln polymorphism may contribute to the risk of developing prostate cancer in African descendants and Hispanic Caucasians. Further larger and well-designed studies are warranted to evaluate this association in detail.

MSMB gene rs10993994 polymorphism increases the risk of prostate cancer.

Genome-wide association studies (GWASs) identified microseminoprotein-ß (MSMB) gene rs10993994 polymorphism was significantly associated with prostate cancer (PC) risk. However, the association between MSMB gene rs10993994 polymorphism and PC risk remains controversial. Therefore, we performed a systematic review and meta-analysis by searching in the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 11 publications containing 13 case-control studies for rs10993994 polymorphism were included in our analysis. Our data indicated that MSMB gene rs10993994 polymorphism was associated with an increased risk of PC. Stratification analyses of ethnicity suggested rs10993994 polymorphism increased the risk of PC among Caucasians, but not among Asians. In conclusion, this meta-analysis indicates that MSMB gene rs10993994 polymorphism increases the risk of PC.

TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of rheumatoid arthritis.

Accumulating evidences suggested that tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs10499194, rs13207033 polymorphisms may be associated with the risk of rheumatoid arthritis (RA). However, these studies yielded contradictory findings. To clarify convincing associations, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 13 case-control studies for rs10499194 polymorphism and 6 studies for rs13207033 polymorphism were included. Our data indicated that TNFAIP3 gene rs10499194, rs13207033 polymorphisms were associated with the decreased risk of RA. Stratification analyses of ethnicity indicated rs10499194, rs13207033 polymorphisms decreased the risk of RA among Caucasian populations, but not among Asian populations. In conclusion, this meta-analysis indicates that TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of RA, especially among Caucasian populations.

Association of IL12B Gene Polymorphisms with Rheumatoid Arthritis: A Meta-analysis.

BACKGROUND AND AIMS: Currently published papers regarding the relationship between interleukin (IL)-12B gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the IL-12B gene polymorphisms (rs3122227 and rs6887695) and RA risk. METHODS: We searched PubMed, Embase, the Cochrane Library and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess associations between IL12B gene polymorphisms and RA. RESULTS: A total of eight publications (4,409 cases and 5,591 controls) were included in this meta-analysis. The results demonstrated that rs3122227 and rs6887695 were not associated with RA risk based on current included studies. However, stratification analyses indicated rs6887695 was associated with RA in Asian patients. Rs3122227 was not related with RA in Asian or Caucasian patients. CONCLUSIONS: Our data indicated that IL-12B gene polymorphisms were not related with RA. However, rs6887695 was associated with RA in Asian patients. Further larger-scale studies are urgently needed to identify the association between IL-12B gene polymorphisms and RA in Asian populations.

Updated meta-analysis of the TP53 Arg72Pro polymorphism and gastric cancer risk.

OBJECTIVE: The p53 tumor suppressor pathway plays an important role in gastric cancer (GC) development. Auto-regulatory feedback control of p53 expression is critical to maintaining proper tumor suppressor function. So far, several studies between p53 Arg72Pro polymorphism and GC have generated controversial and inconclusive results. METHODS: To better assess the purported relationship, we performed a meta-analysis of 19 publications. Eligible studies were identified by searching the Pubmed database. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess any link. RESULTS: Overall, a significant association was detected between the p53 Arg72Pro polymorphism and GC risk (Pro-allele vs. Arg-allele: OR=1.05, 95%CI=1.01-1.08; Pro/Pro vs. Arg/Arg: OR=1.13, 95%CI=1.04-1.22). Moreover, on stratified analysis by race, significantly increased risk was found for Asian populations (Pro-allele vs. Arg-allele: OR=1.06, 95%CI=1.02-1.10; Pro/Pro vs. Arg/Arg: OR=1.16, 95%CI=1.07-1.26; Pro/Pro+Pro/Arg vs. Arg/Arg: OR=1.58, 95%CI=1.09-2.27). CONCLUSIONS: Our study provided evidence that the p53 72Pro allele may increase GC risk in Asians. Future studies with larger sample size are warranted to further confirm this association in more detail.

Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis.

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. METHODS: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS: Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR=1.11, 95%CI=1.03-1.19; TT vs. CC: OR=1.24, 95%CI=1.09-1.41; TC vs. CC: OR=1.11, 95%CI=1.03-1.20 and TT+TC vs. CC: OR=1.09, 95%CI=1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. CONCLUSIONS: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.