Three Polymorphisms of Vascular Endothelial Growth Factor (+936C &gt; T, −460C &gt; T, and −2578C &gt; A) and Their Susceptibility to Ovarian Cancer

Zhang, Xiaolian; Qin, Junqi; Qin, Aiping

doi:10.1097/igc.0000000000000439

Cited by 5 publications

(4 citation statements)

References 40 publications

(26 reference statements)

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“…While the present meta-analysis was being conducted, Zhang et al [ 33 ] published a meta-analysis of the relationship between ovarian cancer risk and the three polymorphisms +936C/T, −460C/T, and −2578C/A. Similar to their results, we found that the CT genotype at +936C/T may act as a protective factor in Caucasian populations.…”

Section: Discussionsupporting

confidence: 87%

Association of four genetic polymorphisms in the vascular endothelial growth factor-A gene and development of ovarian cancer: a meta-analysis

2017

Oncotarget

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This study meta-analyzed the literature on possible association of four polymorphisms (+936C/T, −460C/T, −2578C/A and −1154G/A) in the vascular endothelial growth factor (VEGF)-A gene with risk of ovarian cancer. Meta-analysis of 7 case-control studies involving +936C/T, 4 studies involving −460C/T, 4 studies involving −2578C/A and 2 studies involving −1154G/A showed significant association between −460C/T and ovarian cancer risk. This risk was observed in the total population (allelic model, OR 1.80, 95% CI 1.26–2.59, P = 0.001; recessive model, OR 1.84, 95% CI 1.13–2.98, P = 0.01; dominant model, OR 0.51, 95% CI 0.39–0.67, P < 0.001; homozygous model, OR 2.48, 95% CI 1.72–3.56, P < 0.001; heterozygous model, OR 1.67, 95% CI 1.26–2.21, P < 0.001) and in the subgroup of Asian study participants. The CA genotype at −2578C/A was a risk factor in the total population, while the CT genotype at +936C/T was a protective factor in Caucasians. None of the five genetic models suggested a significant association between −1154G/A and ovarian cancer risk in the entire study population, or between +936C/T and risk in Asian or Chinese participants. These findings should be verified in large, well-designed studies.

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Section: Discussionsupporting

confidence: 87%

Association of four genetic polymorphisms in the vascular endothelial growth factor-A gene and development of ovarian cancer: a meta-analysis

2017

Oncotarget

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“…While such analyses have limitations, they can provide direction for future research ( 25 ). In the results from a newly published meta-analysis ( 26 ) the interaction between three different VEGF polymorphism variants and decreased risk for ovarian cancer was explored. It was concluded that one of these (VEGF +936>T) may be a protective factor for epithelial ovarian cancer among the white ethnicity.…”

Section: Discussionmentioning

confidence: 99%

The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I–II

Skírnisdóttir

Seidal

Åkerud

2016

International Journal of Oncology

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The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I–II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53−/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

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“…[91] As for ovarian, gastric, oral, and prostate cancers, there is no evidence of VEGF-460 being related to them. [86,89,90,92] A meta-analysis of VEGF-460 and overall cancer susceptibility was reported in 2009 by Xu et al [79] They concluded that this SNP could contribute to elevated cancer risk in Asian populations. Most of the above meta-analysis conclusions were consistent with ours, but only for single cancer and less included literature.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigators have conducted meta-analyses to evaluate this link comprehensively. [79][80][81][82][83][84][85][86][87][88][89][90][91][92] Their meta-analysis was almost only for single cancer with small sample sizes. As far as we know, only one meta-analysis of VEGF-460 polymorphisms and overall cancer risk has been published, [79] but it was published earlier and included less studies.…”

Section: Introductionmentioning

confidence: 99%

The relationship between VEGF-460(T>C) polymorphism and cancer risk: A systematic review and meta-analysis based on 46 reports

et al. 2023

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Background: Extensive studies on the link between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) and various malignancy risks produced conflicting results, notably for VEGF-460(T/C). To evaluate this correlation more comprehensively and accurately, we perform a meta-analysis. Methods: Through retrieving 5 databases (Web of Science (WoS), Embase, Pubmed, Wanfang database (Wangfang), and China National Knowledge Infrastructure (CNKI)) and applying hand search, citation search, and gray literature search, 44 papers included 46 reports were enrolled. To evaluate the relationship between VEGF-460 and cancer risk, we pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Our results indicated that the VEGF-460 polymorphism is not related to malignancy susceptibility (dominant model, OR = 0.98, 95% CI = 0.87–1.09; recessive model, OR = 0.95, 95% CI = 0.82–1.10; heterozygous model, OR = 0.99, 95% CI = 0.90–1.10; homozygous model, OR = 0.92, 95% CI = 0.76–1.10; additive model, OR = 0.98, 95% CI = 0.90–1.07). While, in subgroup analysis, this SNP may reduce the risk of hepatocellular carcinoma. Conclusion: this meta-analysis indicated that VEGF-460 was irrelevant to overall malignancy risk, but it might be a protective factor for hepatocellular carcinoma.

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Three Polymorphisms of Vascular Endothelial Growth Factor (+936C > T, −460C > T, and −2578C > A) and Their Susceptibility to Ovarian Cancer

Abstract: This meta-analysis provides supportive evidence that the VEGF +936 C/T polymorphism may influence the risk for the development of OC in a protective model among whites.

Cited by 5 publications

References 40 publications

Association of four genetic polymorphisms in the vascular endothelial growth factor-A gene and development of ovarian cancer: a meta-analysis

Association of four genetic polymorphisms in the vascular endothelial growth factor-A gene and development of ovarian cancer: a meta-analysis

The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I–II

The relationship between VEGF-460(T>C) polymorphism and cancer risk: A systematic review and meta-analysis based on 46 reports

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