Vascular Endothelial Growth Factor +936C/T and +405G/C Polymorphisms and Cancer Risk: a Meta-analysis
Department of Respiratory Medicine, The Affiliated Hospital-School of Medicine, Ningbo University, Ningbo, China. Archives of medical research
(Impact Factor: 2.65).
10/2010; 41(7):548-57. DOI: 10.1016/j.arcmed.2010.09.006
A number of investigators have studied the possible association between vascular endothelial growth factor (VEGF) polymorphisms and cancer risk, but the results have been conflicting. To examine the risk of cancer associated with the +936C/T and +405G/C polymorphisms of VEGF, all available studies were considered in the present meta-analysis.
We performed a computerized search of PubMed and Embase database for relevant studies. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.
Overall, the 936C allele showed no significant effect on cancer risk compared with the 936T allele in all subjects (OR = 0.77, 95% CI = 0.53-1.14; random model). Similarly, no significant effect of 405G allele compared with 405C on cancer risk was found (OR = 1.08, 95% CI = 0.94-1.24; random model). It indicated that the VEGF +936C/T and +405G/C polymorphisms might not be risk factors for cancer, but the 936C allele was associated with a decreased risk of oral cancer (OR = 0.72, 95% CI = 0.53-0.97; fixed model).
The evidence from our meta-analysis supports that there was an association between 936C allele and decreased oral cancer risk, although no evidence of association between VEGF +936C/T or +405G/C polymorphism and cancer was observed in all examined patients. Further studies based on larger, stratified population are required to explore the role of VEGF polymorphisms on cancer risk.
Available from: PubMed Central
- "Kaplan-Meier mortality curves were created to exhibit differences in mortality by selected risk factors. Quantitative synthesis of all relevant studies was performed and the methods used have been described in detail in previous studies (16,17). The HRs of time-to-event data were directly extracted from the original study or were read off survival curves to estimate the logHR and its variance, as suggested by Parmar et al(18). "
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ABSTRACT: The present study aimed to evaluate whether circulating C-reactive protein (CRP) levels are a biomarker of systemic inflammation and a significant predictor of future chronic obstructive pulmonary disease (COPD) outcome. During the study, 116 patients with stable COPD and 35 age- and gender-matched healthy subjects with normal pulmonary function were observed. Patient follow-up was also performed to evaluate the strength of the associations between CRP levels and future outcomes. The observations from the present study showed that serum CRP levels were significantly higher in stable COPD patients than in control subjects (4.48±0.83 vs. 1.01±0.27 mg/l, respectively; P<0.05). In addition, it was identified that a serum CRP concentration of >3 mg/l is a poor prognostic variable of COPD compared with a CRP concentration of ≤3 mg/l [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.05-6.99; P<0.05]. A quantitative synthesis of four studies including 1,750 COPD patients was performed and statistically similar results were obtained (HR, 1.54; 95% CI, 1.14-2.07; P<0.01). The present study showed that circulating CRP levels are higher in stable COPD patients and, therefore, may be used as a long-term predictor of future outcomes. These observations highlight the importance of high sensitivity CRP assays in patients with stable COPD.
Available from: plosone.org
- "Allele frequency might reflect the natural selection pressures or a balance by other related functional genetic variants and environmental exposures , . Thus, a subgroup analysis by ethnicity was performed in our meta-analyses. "
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ABSTRACT: Several studies have been conducted in recent years to evaluate the risk of type 2 diabetes mellitus (T2DM) and polymorphisms of interleukin (IL)-10. However, the results remain conflicting rather than conclusive. This meta-analysis aimed to summarize the current evidence from case-control studies that evaluated this association.
We carried out a search in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.
10 studies were included in our meta-analysis and systemic review. Our meta-analysis indicated that IL-10 -1082A/G polymorphism was associated with the risk of T2DM (GA vs. AA: OR = 1.21, 95% CI = 1.03-1.14; GA/GG vs. AA: OR = 1.22, 95% CI = 1.05-1.41), whereas there was no association between IL-10 -592C/A (CC/CA vs. AA: OR = 1.07, 95% CI = 0.59-1.93) or -819C/T (CC/CT vs. TT: OR = 0.93, 95% CI = 0.49-1.75) polymorphism and T2DM risk was found in our study.
This meta-analysis provides strong evidence that IL-10 -1082A/G polymorphism associated with risk of T2DM. However, no association of the IL-10 -592C/A or -819C/T polymorphism with T2DM risk was found. Additional well-designed large studies were required for the validation of our results.
Available from: Takao Tamura
- "VEGF and related proteins are critical for development, growth and metastasis of tumors, and their expression levels have been demonstrated to be predictive of resistance to treatment 30-32. Genetic polymorphisms in the promoter region, 5'UTR, and 3'UTR of the VEGF gene are associated with VEGF levels in plasma or tumors, and therefore can be diagnostic, prognostic, and predictive biomarkers for patients with tumors 20-23. "
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ABSTRACT: Background: Reports have been accumulating that genetic properties are predictive of clinical response after and/or toxicity during cancer chemotherapy, but little information is available concerning effects on long-term survival. In this study, 49 Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the effects of genotypes of vascular endothelial growth factor (VEGF) were retrospectively revaluated in terms of prediction of long-term survival.
Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. The VEGF genotypes -1498T/C, -1154G/A, -634C/G, -7C/T, 936C/T, and 1612G/A were evaluated.
Results: The complete response (CR) rate was 46.9% (23/49). The 5-year survival rate was 42.9 % (21/49). There were 7 patients with a CR, but survival of less than 5 years. They died from myocardial infarction (N=1), sudden cardiac death after suffering from heart failure (N=1), acute myeloid leukemia that developed from myelodysplastic syndromes (N=1), factors not specified (N=2), oropharynx cancer (N=1), and tongue cancer (N=1). VEGF -634C/G had no effect on clinical response, but long-term survival depended on the genotype (p=0.033, Fisher's; p=0.038, Cochran-Armitage; p=0.079, Log-rank). The genotype frequency of 7 patients with a CR, but survival of less than 5 years was different from that for the other 42 patients (p=0.032, Fisher's). None of the other 5 genotypes evaluated affected either clinical response or survival.
Conclusions: VEGF -634C/G is possibly predictive of long-term survival after treatment with a definitive 5-FU/CDDP-based CRT. Further clinical studies with a larger number of cases are needed to clarify the effects of this genotype.
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