RESUMEN
Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.
Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias de la Mama/genética , Glioma/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas/genética , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/metabolismo , Neoplasias de la Mama/etnología , Neoplasias de la Mama/metabolismo , Metilación de ADN , Femenino , Ácido Fólico/metabolismo , Predisposición Genética a la Enfermedad , Glioma/etnología , Glioma/metabolismo , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Neoplasias Gástricas/etnología , Neoplasias Gástricas/metabolismoRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Glioma/genética , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Glioma/diagnóstico , Glioma/etnología , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
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.
Asunto(s)
Neoplasias Encefálicas/genética , Proteínas de la Matriz Extracelular/genética , Predisposición Genética a la Enfermedad , Glioma/genética , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Glioma/diagnóstico , Glioma/etnología , Glioma/patología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de RiesgoRESUMEN
The association between the CCDC26 rs4295627 single nucleotide polymorphism (SNP) and the glioma risk has been studied previously, but these studies have yielded conflicting results. The aim of the present study is to analyze this association more vigorously, by means of a meta-analysis. A comprehensive literature search was performed in databases PubMed and EMBASE. Six articles including 12 case-control studies in English with 11,368 controls and 5891 cases were eligible for the meta-analysis. We conducted subgroup analyses by the source of controls, ethnicity, and country. Our meta-analysis revealed that the rs4295627 SNP was associated with the glioma risk in a heterozygote model (TG versus TT: odds ratio = 1.35, 95% confidence interval = 1.26-1.45, P = 0.066). Moreover, our results suggested that the rs4295627 SNP was associated with a notably increased risk of glioma among Caucasians except for Swedes in 4 models (the homozygote model, recessive model, dominant model, and additive model). Nonetheless, in Sweden and China, the results showed no associations. No evidence of the publication bias was uncovered. Thus, our meta-analysis suggests that the rs4295627 SNP is associated with an increased risk of glioma. Additional studies are needed to derive more precise conclusion.
Asunto(s)
Neoplasias Encefálicas/genética , Glioma/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Polimorfismo de Nucleótido Simple , Neoplasias Encefálicas/etnología , Estudios de Casos y Controles , China , Glioma/etnología , Humanos , ARN Largo no Codificante , SueciaRESUMEN
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.
Asunto(s)
Neoplasias Encefálicas/genética , Reparación del ADN , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Glioma/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Pueblo Asiatico , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Genotipo , Glioma/etnología , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Análisis de Secuencia de ADNRESUMEN
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.