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

ABSTRACT: 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.

SUBMITTER: Xu CH

PROVIDER: S-EPMC5641192 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Xu Chao-Huan CH He Zhong-Hui ZH Xu Hong H

Oncotarget 20170821 42

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 ...[more]

PMID: 29069849

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Project description:BACKGROUND:Polycystic ovarian syndrome (PCOS) is a multi-gene hereditary disorder caused by the interaction of certain gene variation with environmental factors. Previous studies have shown that vascular endothelial growth factor (VEGF) gene polymorphisms are associated with the risk of polycystic ovarian syndrome. However, the results of these studies remain controversial. We performed the present meta-analysis aiming to further investigate the potential relationship between VEGF polymorphisms and susceptibility to PCOS. METHODS:The following databases were systematically searched: PubMed, EMBASE, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), and Wanfang Databases. The correlation between VEGF polymorphisms and PCOS risk was assessed by calculating pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity and source of control were also conducted. Besides, trial sequential analysis (TSA) was done to verify the reliability of the pooled results. RESULTS:10 relevant case-control studies were incorporated in this meta-analysis, involving 1347 PCOS cases and 1378 controls. The VEGF rs2010963 polymorphism was associated with decreased PCOS risk in the whole population and the Asian populations. The VEGF rs3025039 polymorphism was associated with decreased PCOS susceptibility and the Asian populations, but increased risk of PCOS was observed among the Caucasian populations. In addition, the results of trial sequential analysis (TSA) showed the negative correlation between rs2010963 and PCOS risk, obtained by our meta-analysis, was stable and reliable. CONCLUSION:Overall, different VEGF gene polymorphisms may exert different effects on PCOS susceptibility. The VEGF rs2010963 polymorphism decreases PCOS susceptibility in both the whole population and the Asian populations, and VEGF rs3025039 polymorphism causes lower PCOS susceptibility in the whole population and the Asian populations but higher in the Caucasian populations.

Project description:BackgroundCoronary heart disease (CHD) is a cardiovascular disease characterized by high morbidity and mortality. Vascular endothelial growth factor (VEGF) and its receptor, named kinase insert domain-containing receptor (KDR, or VEGFR2), which are involved with angiogenesis and vascular repair, could partly contribute to the development of CHD. The aim of this study, therefore, was to investigate the potential correlations between genetic polymorphisms on VEGF and KDR and susceptibility to CHD, and the integrative role of SNPs combined on susceptibility to CHD were also studied.Material/methodsVenous blood samples gathered from 533 DCM patients and 533 healthy controls were used to genotype tag-SNPs of VEGF (rs699947, rs2010963, and rs3025010) and KDR (rs2071559, rs2305948, and rs1870377) by polymerase chain reaction (PCR) and SNaPshot assay. Investigations of potential haplotypes were conducted on the basis of SHEsis software. The odds ratio (ORs) and relevant 95% confidence intervals (95% CI) were used to estimate associations of SNPs/haplotypes with risk of CHD. Multivariate logistic regression was also performed, taking certain clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension) into consideration. All statistical analyses were done with STATA Version 12.0 software.ResultsOur results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05-1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01-1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02-1.43, P=0.029; OR=2.54, 95% CI: 1.13-5.75, P=0.025); OR=2.83, 95% CI: 1.47-5.46, P=0.002, respectively). Additionally, haplotype analyses revealed that integration of 5 SNPs would either raise (e.g. C-C-T-G-T and T-G-T-G-T) or reduce (e.g. C-C-C-G-T, T-C-T-G-A, T-C-T-G-T, and T-G-T-G-A) risk of CHD.ConclusionsGenetic polymorphisms on VEGF (rs699947) and KDR (rs2305948and rs1870377), as well as relevant haplotypes, may serve as genetic markers that might be useful in future investigations on the pathogenesis of CHD.

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

Publications

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

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