RESUMO
Glioblastoma (GBM), an aggressive form of brain cancer, has a higher incidence in non-Hispanics when compared to the US Hispanic population. Using data from RT-PCR analysis of 21 GBM tissue from Hispanic patients in Puerto Rico, we identified significant correlations in the gene expression of focal adhesion kinase and proline-rich tyrosine kinase (PTK2 and PTK2B) with NGFR (nerve growth factor receptor), PDGFRB (platelet-derived growth factor receptor B), EGFR (epithelial growth factor receptor), and CXCR1 (C-X-C motif chemokine receptor 1). This study further explores these correlations found in gene expression while accounting for sex and ethnicity. Statistically significant (p < 0.05) correlations with an r value > ±0.7 were subsequently contrasted with mRNA expression data acquired from cBioPortal for 323 GBM specimens. Significant correlations in Puerto Rican male patients were found between PTK2 and PTK2B, NGFR, PDGFRB, EGFR, and CXCR1, which did not arise in non-Hispanic male patient data. The data for Puerto Rican female patients showed correlations in PTK2 with PTK2B, NGFR, PDGFRB, and EGFR, all of which did not appear in the data for non-Hispanic female patients. The data acquired from cBioPortal for non-Puerto Rican Hispanic patients supported the correlations found in the Puerto Rican population for both sexes. Our findings reveal distinct correlations in gene expression patterns, particularly involving PTK2, PTK2B, NGFR, PDGFRB, and EGFR among Puerto Rican Hispanic patients when compared to non-Hispanic counterparts.
Assuntos
Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Hispânico ou Latino , Transdução de Sinais , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/etnologia , Receptores ErbB/genética , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glioblastoma/genética , Glioblastoma/etnologia , Hispânico ou Latino/genética , Porto Rico , Transdução de Sinais/genéticaRESUMO
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.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Glioma/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Metilação de DNA , Feminino , Ácido Fólico/metabolismo , Predisposição Genética para Doença , Glioma/etnologia , Glioma/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/metabolismoRESUMO
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.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Glioma/diagnóstico , Glioma/etnologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
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.
Assuntos
Neoplasias Encefálicas/genética , Proteínas da Matriz Extracelular/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Glioma/diagnóstico , Glioma/etnologia , Glioma/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
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.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Encefálicas/etnologia , Estudos de Casos e Controles , China , Glioma/etnologia , Humanos , RNA Longo não Codificante , SuéciaRESUMO
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.
Assuntos
Neoplasias Encefálicas/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Glioma/etnologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Análise de Sequência de DNARESUMO
OBJECTIVE: To evaluate evidence for differences in pediatric brain tumor diagnoses by race and ethnicity using a cross-sectional study design in individuals with neurofibromatosis type 1 (NF1). STUDY DESIGN: Subjects with NF1 were ascertained from the NF1 Patient Registry Initiative and through a clinical record database of patients at a large academic medical center. Logistic regression was employed to calculate ORs and 95% CIs to analyze differences in the odds of brain tumor diagnosis by race (White, Black, Asian, other/unknown) and ethnic (Hispanic vs non-Hispanic) groups. RESULTS: Data from a total of 1546, 629, and 2038 individuals who were ascertained from the NF1 Patient Registry Initiative, clinical records, and pooled datasets were analyzed, respectively. After adjusting for birth year, we observed a significantly reduced odds of brain tumor diagnoses in individuals self-identified or clinically reported as Black (OR = 0.13, 95% CI 0.05-0.31), Asian (OR = 0.15, 95% CI 0.04-0.64), and other/unknown (OR = 0.61, 95% CI 0.41-0.93) race compared with those with reported as White race. There was no significant difference in the odds of pediatric brain tumor diagnosis by Hispanic ethnicity. CONCLUSIONS: Consistent with prior smaller studies, these data suggest that pediatric brain tumor diagnoses vary by race in individuals with NF1. Reasons underlying observed differences by race warrant further investigation.
Assuntos
Neoplasias Encefálicas/etnologia , Neurofibromatose 1/etnologia , Neoplasias Encefálicas/diagnóstico , Criança , Estudos Transversais , Etnicidade , Feminino , Humanos , Modelos Logísticos , Masculino , Neurofibromatose 1/diagnóstico , Sistema de RegistrosRESUMO
Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C>A and c.-216G>T) and the c.2073A>T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A>T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A>T polymorphism could play a role in future therapeutic approaches to astrocytoma.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Polimorfismo Genético , Adulto , Idoso , Alelos , Astrocitoma/etnologia , Neoplasias Encefálicas/etnologia , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Resultado do TratamentoRESUMO
OBJECTIVE: To determine with greater precision the map location of the locus associated with familial cavernous hemangiomas. BACKGROUND: Cavernous malformations of the brain are a significant cause of seizures, progressive or apoplectic neurologic deficit, and headache. Prevalence estimates from autopsy series vary from 0.39 to 0.9%. This disorder (OMIM #116860) can be inherited as an autosomal dominant trait with variable penetrance. Linkage to markers on the long arm of chromosome 7 was recently reported in separate reports in three apparently unrelated Hispanic kindreds as well as in two kindreds of non-Hispanic descent. DESIGN/METHODS: We examined clinically, by MRI scanning, and by pathologic examination of surgical specimens, members of four large Mexican-American families segregating cavernous hemangiomas of the brain. Linkage analysis was performed with use of blood specimens from morphologically proven cases. Two-point linkage analysis was performed with the MLINK program of the LINKAGE package. Multipoint analysis was performed between two markers and the disease locus with LINKMAP in the FASTLINKAGE package. Allele frequencies were set as described by the Genome Database (GDB). Maximum penetrance for the disease allele was set to 0.75. RESULTS: The highest lod score was observed for marker D7S652 with Zmax = 6.66 at theta(max) = 0.00. Multipoint LOD score analysis placed the disease locus in the 11 cM interval between markers D7S630 and D7S527 with Zmax = 9.19. Haplotype analysis is in agreement with the placement of the disease gene between D7S630 and D7S527 and further shows a minimal shared region within this interval, indicating a founder effect in the establishment of the mutation in these families. CONCLUSIONS: We confirmed the linkage of cavernous hemangioma to markers on the long arm of chromosome 7q, and the estimate of the map location has been refined to a region of shared haplotype between markers D7S630 and D7S527 in four Mexican-American families who may be descended from a common ancestor in Sonora County, Mexico.