BACKGROUND Vascular endothelial growth factor (VEGF) is the key regulator of angiogenesis in the development of various cancers. Previous studies have examined the relationship between VEGF gene promoter polymorphisms such as -2578C/A and -460C/T and bladder cancer risk; however, these results are inconclusive. Therefore, we performed this meta-analysis to investigate the association between VEGF gene promoter polymorphisms and bladder cancer risk. METHODS PubMed, Embase, Cochrane Library and Web of Science databases were searched for studies published before September 2018. The methodological quality assessment of included studies was performed based on the Newcastle-Ottawa Quality Scale (NOS). We conducted a systematic review and meta-analysis using both fixed- and random-effect model. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the relationship. In addition, the stability of our analysis was evaluated by heterogeneity, sensitivity, subgroup of ethnicity, and publication bias analysis. RESULTS We finally included 7 case-control studies with a total of 2412 bladder cancer patients and 3157 cancer-free controls. In Asian population with the VEGF -2578C/A polymorphism, significantly higher bladder cancer risks of 1.55 (95% CI = 1.25-1.93) and 1.53 (95% CI = 1.11-2.10) were found in the heterozygous model (AC vs CC) and the dominant model (AA + AC vs CC), respectively. Though there was no statistical association between VEGF -460C/T polymorphism and bladder cancer, a tendency to higher bladder cancer risk was observed in various genetic models (T vs C; TT vs CC; TC vs CC and TT + TC vs CC). CONCLUSIONS Our findings suggest that VEGF -2578C/A polymorphism might be a risk factor with a modest significance for bladder cancer only in Asian population. Further studies with a larger sample size and other functional polymorphisms are needed to explore the effects of VEGF gene on the risk of bladder cancer.

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VEGF 基因启动子多态性与膀胱癌的关联：一项更新的荟萃分析

背景血管内皮生长因子(VEGF)是各种癌症发展中血管生成的关键调节剂。之前的研究考察了-2578C/A和-460C/T等VEGF基因启动子多态性与膀胱癌风险的关系；然而，这些结果尚无定论。因此，我们进行了这项荟萃分析以研究 VEGF 基因启动子多态性与膀胱癌风险之间的关联。方法 在 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中搜索 2018 年 9 月之前发表的研究。根据纽卡斯尔-渥太华质量量表 (NOS) 对纳入研究进行方法学质量评估。我们使用固定和随机效应模型进行了系统评价和荟萃分析。计算具有 95% 置信区间 (CI) 的汇总优势比 (OR) 以评估关系的强度。此外，我们分析的稳定性通过异质性、敏感性、种族亚组和发表偏倚分析进行评估。结果 我们最终纳入了 7 个病例对照研究，共有 2412 名膀胱癌患者和 3157 名无癌对照。在具有 VEGF -2578C/A 多态性的亚洲人群中，在杂合模型（AC 与 CC）中发现显着更高的膀胱癌风险，分别为 1.55（95% CI = 1.25-1.93）和 1.53（95% CI = 1.11-2.10）和主导模型（AA + AC vs CC），分别。尽管 VEGF -460C/T 多态性与膀胱癌之间没有统计学关联，但在各种遗传模型（T vs C；TT vs CC；TC 对 CC 和 TT + TC 对 CC）。结论 我们的研究结果表明，VEGF -2578C/A 多态性可能是仅在亚洲人群中对膀胱癌具有中等意义的危险因素。需要更大样本量和其他功能多态性的进一步研究来探索VEGF基因对膀胱癌风险的影响。