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This case-control study aimed to investigate the association between PHLDB1 rs498872 polymorphism and the risk of glioma in a Chinese Han population. A total of 210 patients and 235 controls were enrolled in this study. The CT genotype and TT genotype were significantly associated with the risk of glioma (OR=1.48, 95%CI 1.00-2.19, P=0.05 and OR=2.40, 95%CI 1.06-4.10, P=0.03), respectively. In addition, T allele of PHLDB1 rs498872 polymorphism was significantly associated with an increased risk of glioma (OR=1.58, 95%CI 1.08-2.29, P=0.02). We also found that PHLDB1 rs498872 polymorphism was not associated with histology and tumor grade of glioma. In conclusion, this study found that PHLDB1 rs498872 polymorphism was significantly associated with glioma risk in Chinese Han population.

Aims: To investigate the impact of CCND1 and EFEMP1 gene polymorphism, and additional their gene-gene interactions and haplotype within EFEMP1 gene on glioma risk based on Chinese population., Methods: Logistic regression was performed to investigate association between single-nucleotide polymorphisms (SNP) and glioma risk and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interaction., Results: Glioma risks were higher in carriers of homozygous mutant of rs603965 within CCND1 gene, rs1346787 and rs3791679 in EFEMP1 gene than those with wild-type homozygotes, OR (95%CI) were 1.67 (1.23-2.02), 1.59 (1.25-2.01) and 1.42 (1.15-1.82), respectively. GMDR analysis indicated a significant two-locus model (p=0.0010) involving rs603965 within CCND1 gene and rs1346787 within EFEMP1 gene. Overall, the cross-validation consistency of the two- locus models was 10\ 10, and the testing accuracy is 60.17%. Participants with rs603965 - GA or AA and rs1346787- AG or GG genotype have the highest glioma risk, compared to participants with rs603965 - GG and rs1346787- AA genotype, OR (95%CI) was 3.65 (1.81-5.22). We conducted haplotype analysis for rs1346787 and rs3791679, because D' value between rs1346787 and rs3791679 was more than 0.8. The most common haplotype was rs1346787 - A and rs3791679- G haplotype, the frequency of which was 0.4905 and 0.4428 in case and control group., Conclusions: Polymorphism in rs603965 within CCND1 gene and rs1346787 within EFEMP1 gene and its gene- gene interaction were associated with increased glioma risk.

We conducted a study in a Chinese Han population to investigate the role of XRCC1 gene polymorphisms (Arg399Gln and Arg194Trp) with a risk of susceptibility to gliomas. Samples from 115 patients with gliomas and 228 control subjects were consecutively collected between March 2012 and December 2014. Genotype analysis of XRCC1 Arg399Gln and Arg194Trp was performed using polymerase chain reaction-restriction fragment length polymorphism assay. All the analyses were performed using the SPSS 17.0 software package. We observed that the XRCC1 Arg399Gln and Arg194Trp genotype frequencies conformed to the Hardy-Weinberg equilibrium. We observed that the Trp/Trp genotype of XRCC1 Arg194Trp was associated with an increased risk of glioma when compared to the wild-type genotype (odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.14-3.86, P = 0.03). In the dominant model, we found that the Arg/Trp + Trp/Trp genotype of XRCC1 Arg194Trp could significantly elevate the susceptibility of developing glioma (OR = 1.79, 95%CI = 1.07-0.94). However, we observed that the XRCC1 Arg399Gln genetic polymorphism did not influence the risk of glioma. In summary, we suggest that the XRCC1 Arg194Trp genetic polymorphism could be a predictive biomarker for the susceptibility to glioma in a Chinese population., Competing Interests: The authors declare no conflict of interest.

In this study, we assessed the association between the EFEMP1 rs3791679 polymorphism and glioma risk in a Chinese Han population. A total of 94 glioma patients and 206 healthy controls who conformed to the inclusion and exclusion criteria were recruited from Baogang Hospital between March 2012 and October 2014. The EFEMP1 rs3791679 gene polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism assay and the results were statistically analyzed using SPSS Statistics 17.0. The results of unconditional logistic regression analysis revealed that the GG genotype of EFEMP1 rs3791679 was positively correlated with increased susceptibility to glioma (adjusted OR = 2.09, 95%CI = 1.21-7.81). Moreover, the GG genotype of EFEMP1 rs3791679 was correlated with higher risk of glioma compared to the AA+GA genotype (OR = 2.60, 95%CI = 1.08-6.28) in the regressive model. In conclusion, we report that the EFEMP1 rs3791679 polymorphism influences glioma susceptibility in the Chinese Han population., Competing Interests: The authors declare no conflict of interest.

So far, epidemiological studies have been performed to investigate the association of CDKN2A/B rs4977756 polymorphism and glioma risk. However, the results from different studies remain inconsistent. To clarify these conflicts and to quantitatively evaluate the effect of rs4977756 polymorphism on glioma risk, a meta-analysis was conducted using relevant published clinical studies about rs4977756 polymorphisms and glioma risk. Relevant studies concerning the association between rs4977756 polymorphism and risk of glioma were included in this meta-analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated under fixed or random effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included 13 studies with a total of 8129 cases and 15,858 controls. The pooled results showed that there was an obvious association of CDKN2A/B rs4977756 polymorphism with risk of glioma in all four comparison models (dominant model/AG + GG vs. AA: OR = 1.36, 95 %CI = 1.20-1.54, p < 0.01; heterozygote comparison/AG vs. AA: OR = 1.31, 95 %CI = 1.12-1.53, p < 0.01; homozygote comparison/GG versus AA: OR = 1.49, 95 %CI = 1.36-1.64, p < 0.01; additive model/G vs. A: OR = 1.23, 95 %CI = 1.18-1.28, p < 0.01, respectively). For the subgroup analyses of ethnicities, similar results were observed in Caucasians. However, the association was not found between rs4977756 polymorphism and the risk of glioma in all models for the Asian studies. The CDKN2A/B rs4977756 polymorphism is obvious increase the risk of glioma in Caucasians. Future studies are needed to confirm the results in other ethnic populations.

The susceptibility to glioma is not well understood. It has been suggested that the X-ray cross complementing group 3 (XRCC3) gene influences the capacity to repair DNA damage, leading to increased glioma susceptibility. In this study, we evaluated the relationship between XRCC3 mutations and glioma risk. Genotypes were assessed in 389 Chinese glioma patients and 358 healthy controls. XRCC3 Thr241Met (rs861539) and 2 additional polymorphisms, rs3212112 (c.774+19T>G) and rs1799796 (c.562-14A>G), were directly sequenced. The frequency of the rs861539 T allele was significantly lower in the glioma group than in healthy controls [11.1 vs 17.7%, odds ratio = 0.62 (0.48-0.80), P < 0.001]; the frequencies of the CT or CT+TT genotypes differed between groups (18.5 vs 31%, 20.3 vs 33.2%, respectively). The frequency of the rs3212112 G allele was significantly higher in the glioma group than in healthy controls [15.8 vs 5.3%, odds ratio = 2.94 (2.07-4.17), P < 0.001]. The frequencies of the GT or TG+GG genotypes differed between groups (25.4 vs 7.8%, 28.5 vs 9.2%, respectively). This study demonstrates that the rs861539 and rs3212112 polymorphisms in the XRCC3 gene may influence the risk of glioma development in Chinese populations.

Several previous studies indicated that genetic polymorphisms in inflammatory factor genes were associated with glioma risk. However, the relationship between the prostaglandin-endoperoxide synthase 2 (PTGS2) genetic polymorphism and glioma remains unclear in the Chinese population. We selected 199 histologically confirmed adult glioma patients and 199 cancer-free controls for the present study and analyzed the distribution of the PTGS2 genotypes and haplotypes. We found that the CC+CT genotype of rs5275 was common in the control group but not in the glioma group (P = 0.033). In addition, we found that the frequency of the C allele was higher in the control group than in the glioma group (P = 0.014). For rs6681231, although we found no significant difference between the 2 groups in genotype distribution, we found that the frequency of the C allele was lower in glioma patients than in control subjects (P = 0.044). We found no significant difference between these 2 groups in the rs689466 genotype and allele distributions. Haplotype analysis suggested that the frequency of the C-A-C haplotype was significantly lower in glioma patients than in control subjects [P = 0.028, odds ratio (OR) = 0.628, 95% confidence interval (CI) = 0.413-0.955]. However, the frequency of the T-A-G haplotype was higher in glioma patients than in control subjects (P = 0.036, OR = 1.418, 95%CI = 1.022-1.967). Therefore, polymorphisms in the PTGS2 gene may be associated with glioma susceptibility in the Chinese population.

Glioma is the most common type of primary brain tumors in adults. Previous evidence indicates that the X-ray repair cross-complementing group 1 gene (XRCC1) is an important candidate gene which influencing the pathogenesis of glioma. This study aims to assess the potential associations between glioma risks and genetic polymorphisms of XRCC1 gene. A total of 1,286 Chinese Han ethnic subjects consisting of 638 glioma patients and 648 controls were recruited in this case-control study. The genotyping of XRCC1 genetic polymorphisms (c.482C>T, c.1161G>A, and c.1804C>A) were conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods. Our data indicated that the allelic and genotypic frequencies of these genetic polymorphisms in glioma patients were significantly different from those of controls. We detected that the alleles/genotypes were statistically associated with the increased risks of glioma (for c.482C>T, TT versus (vs.) CC: OR = 2.24, 95% CI = 1.48-3.39, P < 0.001; T vs. C: OR = 1.30, 95% CI = 1.09-1.53, P = 0.003; for c.1161G>A, AA vs. GG: OR = 1.62, 95% CI = 1.11-2.35, P = 0.012; A vs. G: OR = 1.19, 95% CI = 1.01-1.41, P = 0.040; for c.1804C>A, AA vs. CC: OR = 2.12, 95% CI = 1.45-3.11, P < 0.001; A vs. C: OR = 1.32, 95% CI = 1.12-1.56, P = 0.001). Our findings suggest that these genetic polymorphisms of XRCC1 gene may influence glioma risks in Chinese Han ethnic subjects, and might be potential molecular markers for evaluating glioma risks., (© 2013 Wiley Periodicals, Inc.)

Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of glioma. A comprehensive search was conducted to identify all case-control studies on the EGF +61A>G polymorphism and glioma risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Statistical analysis was performed with the software program Stata (version 12.0). A total of ten eligible studies, including 1,888 cases and 2,836 controls were included in this work. Overall, there was a significant association between EGF +61A>G polymorphism and glioma risk in the allele model (OR = 1.419, 95% CI = 1.144-1.759, P = 0.001). In the subgroup analysis by ethnicity, significant associations were also found in Asian populations under all different genetic models (homozygote model: OR = 1.727, 95% CI = 1.310-2.275, P = 0.000; heterozygote model: OR = 1.202, 95% CI = 1.023-1.413, P = 0.025; dominant model: OR = 1.279, 95% CI = 1.096-1.491, P = 0.002; recessive model: OR = 1.590, 95% CI = 1.221-2.070, P = 0.001; and A-allele versus G-allele OR = 1.600, 95% CI = 1.145-2.236, P = 0.006). However, no significant associations were found among Caucasians in all comparison models. In conclusion, the results suggest that there is a significant association between EGF +61A>G polymorphism and glioma risk among Asians.

Methylenetetrahydrofolate reductase (MTHFR) gene plays key roles not only in folate metabolism but also in carcinogenesis. The single nucleotide polymorphism MTHFR C677T has been indicated in the development of various tumors. The effect of the MTHFR C677T polymorphism on brain tumors remains poorly understood. We performed the present meta-analysis and aimed to provide a better understanding of the pathogenesis of brain tumors. A literature search of the PubMed, Embase, Web of Science, and Wanfang databases was carried out for potential relevant publications. We calculated the pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) to assess the association of MTHFR C677T with the susceptibility to brain tumors. We also performed stratified analysis and sensitivity analysis to further estimate the genetic association. All statistical analyses were conducted by the use of STATA 11.0 (STATA Corporation, College Station, TX, USA). Eight case-control studies involving a total of 3,059 cases and 3,324 controls were retrieved according to the inclusion criteria. The overall ORs suggested that the MTHFR C677T variant can exert a risk effect on brain tumor development under the following contrast models (OR(TC vs. CC) = 1.14, 95% CI 1.02-1.27, P OR = 0.018; OR(TT + TC vs. CC)= 1.23, 95% CI 1.01-1.51, P(OR) = 0.043). No significant correlation was identified among the Caucasians, but not among the Asians. In addition, the TC genotype carriers were more susceptible to meningioma when compared with the CC genotype carriers (OR(TC vs. CC) = 1.38, 95% CI 1.15-1.65, P(OR) < 0.001). The MTHFR C677T polymorphism seemed to exert no effect on glioma risk. The current meta-analysis firstly provides evidence that the MTHFR C677T polymorphism may modify the risk for brain tumors, particularly meningioma. The role of the MTHFR C677T variant in brain tumor pathogenesis across diverse ethnicities needs further elucidation by more future studies with large sample size.

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G+405C, G-634C) [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.04-1.58; GC/CC vs. GG] and rs3025030 (OR = 2.21; 95% CI = 1.18-4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR = 0.66; 95% CI = 0.47-0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20-40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p = 0.002, p(corrected) = 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (p(trend) = 8.4 × 10(-5) ). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation., (Copyright © 2010 UICC.)

Epidermal growth factor (EGF) plays a key role in survival of neural and glial precursor cells. The +61A/G polymorphism of the EGF gene is located in the 5'-untranslated region of EGF mRNA and may affect DNA folding or gene transcription, leading to the increase in EGF protein expression. The association between the +61G allele and glioma risk has been widely reported; however, in general the data from published studies with individually low statistical power were controversial and underpowered. We conducted a search in the PubMed database without a language limitation, covering all papers published by the end of October 2010. Overall, 6 case-control studies with 1453 glioma cases and 1947 controls were retrieved based on the search criteria for glioma susceptibility related to the +61A/G polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. We found that EGF +61G allele is associated with the low glioma risk in Chinese population [G-allele vs. A-allele, OR = 0.93, 95%CI (0.89-0.97), P(heterogeneity) = 0.318, I² = 0.0], but with the high glioma risk in European population [G-allele vs. A-allele, OR = 1.14, 95%CI (1.04-1.24), P(heterogeneity) = 0.310, I² = 14.6]. In the stratified analysis by source of control, significant association was observed between hospital-based control and glioma risk [homozygote comparison, OR = 1.14, 95%CI (1.02-1.27), P(heterogeneity) = 0.179, I² = 71.8]. In conclusion, EGF +61G allele represents a risk factor for glioma in European population and conversely a protective factor in Chinese population.