| Background:The most common urinary carcinomas are renal cell carcinoma(RCC),bladder carcinoma(BCa)and prostate cancer(PCa).RCC accounts for 2-3% of all adult malignancies [1].Epidemiologically,the incidence of RCC is significantly correlated with region,race,gender,and age [1].It is higher in developed countries than in developing countries,in urban areas than in rural areas and in males than in females[1].The exact etiologies of RCC remain unclear.The following four factors have been demonstrated to be associated with the RCC onset in evidence-based studies:(I)genetics [2];(II)smoking [3];(III)obesity [4];and(IV)hypertension and anti-hypertensive treatment [5].BCa is the most common malignant tumor in urinary system,most of which come from epithelial tissue,of which more than 90% are transitional cell carcinoma.The development of BCa is a complex,multistep,and multifactorial process,and involves multiple environmental and genetic factors.Smoking and long-term exposure to industrial chemicals have been established as strong determinants of risk factors for BCa.The primary risk factor for bladder cancer is cigarette smoking.Smoking can increase the risk of BCa by 2 to 4 times,and the risk rate is proportional to the intensity and time of smoking [6,7].The occurrence of BCa may also be related to heredity [8,9].Patients with positive family history of cancers were significantly prone to suffering from BCa [10,11].The incidence of PCa was significantly different between geographic and ethnic groups,and the incidence rate was the second most common male malignancy in worldwide [12].The risk factors for PCa are not yet known,which have been identified including age,race,and genetics.Genetic variations in angiogenesis-related genes have also been reported to be involved in the etiology of urological cancers.Vascular endothelial growth factor(VEGF),which is well known as an essential factor for vascular permeability,plays an important role in vasculogenesis and angiogenesis.There are a lot of researches on the relationship between VEGF gene polymorphisms and the risk of urologic neoplasms,but the results are not inconsistent completely.Meta-analysis is a method of systematic and quantitative analysis depending on multiple independent studies with the same research purposes,"reprocessing" the raw data.Increasing the sample size by combining multiple researches to overcome the defects that sample size of individual study is small and the results of these studies are inconsistent,in order to obtain more objective and reliable results.Objective:We perform this meta-analysis on pervious published clinical study to evaluate the relationship between VEGF gene-2578C/A(rs699947)polymorphisms and the risk of urologic neoplasms,and to provide evidence-based medicine basis for the etiology and early diagnosis of urologic neoplasms.Methods:Relevant literatures were extensively searched in Pub Med,Embase,Medline,Wanfang Databases,CNKI and VIP for collecting the case-control studies investigating the relationship between VEGF genetic polymorphisms and urologic neoplasms(RCC,BCa,PCa).Odds ratios(OR)with 95% confidence intervals(CI)were applied to assess the strength of association under the homozygote model(AA vs CC),heterozygote model(CA vs CC),dominant model(AA+CA vs CC),recessive model(AA vs CC+CA),and allele model(A vs C).According to different ethnicities,the objects were divided into three subgroups as Asian subgroup,Caucasian subgroup and Mix subgroup to analyze respectively.According to different tumor types,the objects were divided into three subgroups as RCC subgroup,BCa subgroup and PCa subgroup to analyze respectively.The Rev Man5.3 software was applied for heterogeneity test and combined OR and their 95%CI calculation.Publication bias was assessed through funnel plot and Egger's test,and sensitivity analysis was performed through eliminating each case-control study to observe the changes of OR value and the stability of the statistical results to assess the stability of the results.Results:A total of 10 studies that involved eight SNPs of 1858 cases and 2938 controls were included in this meta-analysis.The shapes of funnel plots revealed no evidence of obvious asymmetry,indicating there was no statistical evidence of publication bias.Our meta-analysis showed that:(1)for homozygote model(AA vs CC),there was no statistical significance of overall comparisons [OR(95%CI):1.11(0.79~1.56),P=0.55] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Subgroup analysis showed that,there was no statistical significance of Asian subgroup [OR(95%CI):1.36(0.96~1.93),P=0.08],Caucasian subgroup [OR(95%CI):0.52(0.16~1.73),P=0.29],Mix subgroup [OR(95%CI):1.10(0.56~2.19),P=0.78],BCa subgroup [OR(95%CI):0.73(0.46~1.17),P=0.20] and PCa subgroup [OR(95%CI): 0.47(0.07~3.26),P=0.44] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers;there was statistical significance of RCC subgroup [OR(95%CI): 1.58(1.21~2.07),P < 0.01] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.(2)for heterozygote model(CA vs CC),there was no statistical significance of overall comparisons [OR(95%CI):1.19(0.97~1.45),P=0.09] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Subgroup analysis showed that,there was statistical significance of Asian subgroup [OR(95%CI):1.35(1.02~1.77),P=0.03] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers;there was no statistical significance of Caucasian subgroup [OR(95%CI): 1.03(0.75~1.42),P=0.83],Mix subgroup [OR(95%CI): 0.86(0.60~1.24),P=0.42],RCC subgroup [OR(95%CI):1.30(0.98~1.72),P=0.07],BCa subgroup [OR(95%CI):1.25(0.79~1.98),P=0.34] and PCa subgroup [OR(95%CI):0.88(0.65~1.19),P=0.40] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.(3)for dominant model(AA+CA vs CC),there was no statistical significance of overall comparisons [OR(95%CI):1.17(0.95~1.44),P=0.15] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Subgroup analysis showed that,there was statistical significance of Asian subgroup [OR(95%CI):1.35(1.05~1.75),P=0.02] and RCC subgroup [OR(95%CI):1.35(1.03~1.77),P=0.03] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers;there was no statistical significance of Caucasian subgroup [OR(95%CI):0.93(0.65~1.32),P=0.67],Mix subgroup [OR(95%CI):0.90(0.64~1.26),P=0.53],BCa subgroup [OR(95%CI):1.06(0.64~1.75),P=0.82] and PCa subgroup [OR(95%CI):0.85(0.64~1.13),P=0.27] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.(4)for recessive model(AA vs CC+CA),there was no statistical significance of overall comparisons [OR(95%CI): 1.01(0.77~1.34),P=0.93] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Subgroup analysis showed that,there was no statistical significance of Asian subgroup [OR(95%CI):1.14(0.84~1.53),P=0.40],Caucasian subgroup [OR(95%CI):0.54(0.19~1.56),P=0.25],Mix subgroup [OR(95%CI):1.16(0.59~2.27),P=0.68],BCa subgroup [OR(95%CI):0.75(0.52~1.09),P=0.13] and PCa subgroup [OR(95%CI): 0.48(0.07~3.47),P=0.47] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers;there was statistical significance of RCC subgroup [OR(95%CI): 1.36(1.09~1.69),P < 0.01] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.(5)for allele model(A vs C),there was no statistical significance of overall comparisons [OR(95%CI):1.07(0.91~1.25),P=0.41] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Subgroup analysis showed that,there was statistical significance of Asian subgroup [OR(95%CI):1.20(1.02~1.41),P=0.03] and RCC subgroup [OR(95%CI):1.24(1.06~1.46),P<0.01] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers;there was no statistical significance of Caucasian subgroup [OR(95%CI):0.81(0.53~1.24),P=0.33],Mix subgroup [OR(95%CI):0.95(0.72~1.26),P=0.72],BCa subgroup [OR(95%CI):0.94(0.72~1.23),P=0.66] and PCa subgroup [OR(95%CI):0.81(0.56~1.71),P=0.26] between VEGF gene-2578C/A polymorphism and the risk of urologic cancers.Conclusion:1.There was a significant association between VEGF gene-2578C/A(rs699947)polymorphisms and the risk of urologic cancers(Asian subgroup and RCC subgroup).2.There was no significant association between VEGF gene-2578C/A(rs699947)polymorphisms and the risk of urologic cancers(Caucasian subgroup,Mix subgroup,BCa subgroup and PCa subgroup). |
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