Association between Functional EGF+61 Polymorphism and Glioma Risk (original) (raw)
Related papers
Association between EGF +61 G/A and glioma risk in a Chinese population
BMC Cancer, 2010
Background: Epidermal growth factor (EGF) is critical in cancer process. EGF and EGF receptor (EGFR) interaction plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variations of the EGF +61G/A (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to brain glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population. Methods: In this study, we analyzed single nucleotide polymorphism of EGF +61G/A in 677 patients with glioma and 698 gender-and age-matched controls. Genotyping was performed by polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Results: The A allele (minor Allele) was 33.0% in cases and 27.3% in controls. The additive model was more powerful to reveal the association in our study than that of recessive and dominant model. Our data showed the genotype G/A and A/A was associated with increased risk for glioma (adjusted OR = 1.48, 95%CI: 1.
Association between epidermal growth factor gene rs4444903 polymorphism and risk of glioma
Tumor Biology, 2013
The development of glioma is a complex process which may be influenced by many factors including the epidermal growth factor (EGF) gene polymorphism. Previous studies showed that EGF rs4444903 polymorphism could result in increased risk of tumorigenesis in multiple human cancers, but published data regarding the association between EGF rs4444903 polymorphism and glioma risk were inconsistent. To derive a more precise estimation of the association between EGF rs4444903 polymorphism and glioma risk, we performed a systematic review and meta-analysis of previous published studies. PubMed, Embase, and the Wanfang databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Ten published studies with 1,891 glioma cases and 2,836 controls were finally included into the study. Overall, there was a significant association between EGF rs4444903 polymorphism and glioma risk in all four genetic models (the allele model:
Genetic variations in EGF and EGFR and glioblastoma outcome
Neuro-Oncology, 2010
Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94 -1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99 -1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.
Analysis of EGF+61AG polymorphism and EGF serum levels
Purpose Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF?61A[G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF?61A[G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route. Methods The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n = 196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR-RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival. Results Patients with primary glioblastoma had high frequency of AA genotype (p = 0.037) and A allele (p = 0.037). Increased EGF circulating levels were observed in glioma patients with AA (p = 0.042), AG (p = 0.006), and AA ? AG (p = 0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p [ 0.05) survival rate, and EGF levels lower than 250 pg/mL was consistently (p = 0.0374) associated with increased survival. Conclusion Presence of EGF?61A[G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.
Data from Impact of <i>EGFR</i> Genetic Variants on Glioma Risk and Patient Outcome
2023
Background: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, À216G/T and À191C/A, and a polymorphic (CA) n microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. Methods: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. Results: None of the EGFR À216G/T variants was significantly associated with glioma risk. The À191C/A genotype was associated with higher risk for glioma when the (CA) n alleles were classified as short for 16 or 17 repeats. Independently of the (CA) n repeat cutoff point used, shorter (CA) n repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA) n cutoff points, only À191C/A genotype was consistently associated with improved survival of patients with glioblastoma. Conclusions: Our findings implicate EGFR À191C/A and the (CA) n repeat polymorphisms as risk factors for gliomas, and suggest À191C/A as a prognostic marker in glioblastoma. Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies. Cancer Epidemiol Biomarkers Prev; 20(12); 2610-7. Ó2011 AACR.
A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
Acta Oncologica, 2010
Published text: U Andersson...A Swerdlow, M Schoemaker et al (2010) A comprehensive study of the associationbetween the EGFR and ERBB2 genes and glioma risk, Acta Oncologica, 49(6), 767-775 1 A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. Summary Background: Malignant glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases and their known ligands, exemplified by the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression and affect survival. The purpose of the present study was to evaluate the effects of genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods: We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Findings: Fourteen of the SNPs were significantly associated with glioma risk at p<0.05 and 17 of the SNPs were
Journal of Cancer Research and Clinical Oncology, 2012
Purpose Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF?61A[G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF?61A[G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route. Methods The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n = 196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR-RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival. Results Patients with primary glioblastoma had high frequency of AA genotype (p = 0.037) and A allele (p = 0.037). Increased EGF circulating levels were observed in glioma patients with AA (p = 0.042), AG (p = 0.006), and AA ? AG (p = 0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p [ 0.05) survival rate, and EGF levels lower than 250 pg/mL was consistently (p = 0.0374) associated with increased survival. Conclusion Presence of EGF?61A[G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.
Impact of EGFR Genetic Variants on Glioma Risk and Patient Outcome
Cancer Epidemiology Biomarkers & Prevention, 2011
Background: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, À216G/T and À191C/A, and a polymorphic (CA) n microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. Methods: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. Results: None of the EGFR À216G/T variants was significantly associated with glioma risk. The À191C/A genotype was associated with higher risk for glioma when the (CA) n alleles were classified as short for 16 or 17 repeats. Independently of the (CA) n repeat cutoff point used, shorter (CA) n repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA) n cutoff points, only À191C/A genotype was consistently associated with improved survival of patients with glioblastoma. Conclusions: Our findings implicate EGFR À191C/A and the (CA) n repeat polymorphisms as risk factors for gliomas, and suggest À191C/A as a prognostic marker in glioblastoma. Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies. Cancer Epidemiol Biomarkers Prev; Ó2011 AACR.
Cancer Genetics and Cytogenetics, 2010
Epidermal growth factor can activate several signaling pathways, leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. The EGF protein is involved in nervous system development, and polymorphisms in the EGF gene on chromosome band 4q25 are associated with brain cancers. The purpose of this study was to investigate the association between the single-nucleotide polymorphism of EGF þ 61 G/A and extraaxial brain tumors in a population of the southeast of Brazil. We analyzed the genotype distribution of this polymorphism in 90 patients and 100 healthy subjects, using the polymerase chain reactionerestriction fragment length polymorphism technique. Comparison of genotype distribution revealed a significant difference between patients and control subjects (P ! 0.001). The variant genotypes of A/G and G/G were associated with a significant increase of the risk of tumor development, compared with the homozygote A/A (P ! 0.0001). When the analyses were stratified, we observed that the genotype G/G was more frequent in female patients (P 5 0.021). The same genotype was observed more frequently in patients with low-grade tumors (P 5 0.001). Overall survival rates did not show statistically significant differences. Our data suggest that the EGF A61 G polymorphism can be associated with susceptibility to development of these tumors. Ó
Impact of TGF-β1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis
Tumor Biology, 2015
Transforming growth factor beta (TGF-β) plays an important role in carcinogenesis. Two polymorphisms in the TGF-β1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancer. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study we investigated the relevance of these TGF-β1 polymorphisms in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). The influence of TGF-β1-509C/T and 869T/C polymorphisms on glioma patient survival were evaluated by a Cox regression model adjusted for patients' age and sex, and represented in Kaplan-Meier curves. Our results demonstrated that TGF-β1 gene polymorphisms-509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous-509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC+CT genotypes (OR, 2.41; 95% CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT+TC genotypes (OR, 2.62; 95% CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-β1-509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas, but may be relevant prognostic biomarkers in GBM patients.