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Association of Vascular Endothelial Growth Factor Gene rs25648 Polymorphism and Risk of Bladder Cancer: A Meta-Analysis

血管內皮生長因子rs25648基因多形性與膀胱癌的相關性:統合分析

摘要


Background and Purpose: Vascular endothelial growth factor (VEGF) plays a crucial role in the angiogenesis of bladder cancer. The relationship between VEGF -7C/T (rs25648) polymorphism and risk of bladder cancer was studied extensively in recent years, albeit with ambiguous conclusions. Therefore, we conducted the present systematic review and meta-analysis to evaluate the association between VEGF -7C/T (rs25648) polymorphism and the risk of bladder cancer. Methods: We performed a comprehensive literature search in PubMed, Embase, and Google Scholar databases to identify eligible literature up to February 2019. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. The stability of our analysis was evaluated using heterogeneity, sensitivity, subgroup, and publication bias analyses. Results: Three case-control studies comprising 1,645 patients with bladder cancer and 2,009 controls fulfilling the inclusion and exclusion criteria were selected for this meta-analysis. The pooled ORs for bladder cancer under an allele model (T vs. C) and a dominant model (T/T+C/T vs. C/C) were 1.31 and 1.26, respectively, with no inter-study heterogeneity. Under a recessive model (T/T vs. C/C+C/T), significantly increased bladder cancer risks of 2.34 and 2.44 were determined for the fixed effect and random effects models, respectively. Subgroup analysis revealed significantly increased bladder cancer risks in both Asian and Spanish populations. Conclusion: Our findings suggest that VEGF -7C/T (rs25648) polymorphism is significantly associated with bladder cancer. Nonetheless, further studies with a larger sample size are needed to clarify the effects of VEGF polymorphisms on bladder cancer.

並列摘要


背景及目的:血管內皮生長因子在膀胱癌的血管新生過程中扮演重要的角色。近年來,血管內皮生長因子的基因多形性(例如:rs25648)與膀胱癌的關係雖逐漸受到關注,然而這些研究結果仍然不一致。因此,本研究利用系統性文獻回顧與統合分析的方法進一步釐清血管內皮生長因子的基因多形性(rs25648)與膀胱癌的關係。方法:本研究利用關鍵詞及完整的蒐尋相關文獻資料庫包括PubMed、Embase及Google Scholar找尋符合納入/排除條件的相關文獻納入分析。文獻搜尋期間從過去截至2019年2月。利用統合的危險對比值與百分之九十五信賴區間估計相關性的強度。透過異質性、敏感度、次族群與發表偏誤的分析評估本研究分析結果的穩定性。結果:本研究最後採用3篇符合納入/排除條件的文獻,合計1,645名膀胱癌個案及2,009名對照組個案的資料被萃取並進行統合分析。研究結果顯示在對偶基因(T vs. C)與顯性模式(T/T+C/T vs .C/C)下,帶有“T"對偶基因及“T/T+C/T"基因型者分別有1.31及1.26倍顯著較高罹患膀胱癌的風險。在隱性模式(T/T vs. C/C+C/T)下,帶有“T/T"基因型者在固定效應模型及隨機效應模型下分別具有2.34及2.44倍顯著較高罹患膀胱癌的風險。從次族群分析的結果顯示亞洲與西班牙族群帶有血管內皮生長因子危險基因型者皆有顯著較高的膀胱癌風險。結論:本研究結果發現血管內皮生長因子基因多型性(rs25648)與罹患膀胱癌的風險有顯著相關。未來仍然需要較大型的研究進一步釐清血管內皮生長因子基因多形性在膀胱癌的致癌機轉、治療及預後所扮演的角色。

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