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血管内皮生长因子的五种多态性与肾细胞癌风险之间的关联:一项更新的荟萃分析。

The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis.

作者信息

Wang Jiao, Shen ChangXin, Fu YouRong, Yu Tian, Song JingJing

机构信息

Genetic Diagnosis Center.

Blood Transfusion Department, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.

出版信息

Onco Targets Ther. 2017 Mar 21;10:1725-1734. doi: 10.2147/OTT.S125965. eCollection 2017.

Abstract

BACKGROUND

Vascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study.

MATERIALS AND METHODS

Relevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations.

RESULTS

A total of eight case-control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11-1.72, =0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05-1.39, =0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04-1.57, =0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05-1.40, =0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57-0.98, =0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC risk in our study.

CONCLUSION

Our meta-analysis confirmed the fact that rs699947, rs3025039, and rs10434 polymorphisms were significantly relevant to elevated RCC risk. In the meanwhile, this study also demonstrated that the allele contrast model of rs3025039 polymorphism was likely to be associated with risk of RCC in the Asian population.

摘要

背景

血管内皮生长因子(VEGF)是一种关键介质,在血管生成、肿瘤生长和肿瘤转移中发挥重要作用。VEGF的五个多态性位点(rs3025039、rs699947、rs10434、rs1570360和rs2010963)与肾细胞癌(RCC)风险之间的关联已得到广泛研究,但目前可得的结果并不一致且尚无定论。为了更准确地评估这些关联,我们在本研究中进行了一项荟萃分析。

材料与方法

从以下三个电子数据库系统收集相关研究:MEDLINE、科学网和中国知网(CNKI)。使用RevMan 5.2软件在固定效应或随机效应模型中进行统计分析。计算合并比值比(OR)及其95%置信区间(95%CI)以确定关联强度。

结果

本荟萃分析共纳入八项病例对照研究,其中有1936例RCC病例和2770例对照符合纳入标准。合并OR表明,rs699947多态性在所有遗传模型中均与RCC风险显著相关。rs3025039多态性与RCC风险在纯合子模型(TT vs CC:OR = 1.38,95%CI = 1.11 - 1.72,P = 0.004)、显性模型(CT + TT vs CC:OR = 1.21,95%CI = 1.05 - 1.39,P = 0.01)和隐性模型(TT vs CC + CT:OR = 1.28,95%CI = 1.04 - 1.57,P = 0.02)中也存在显著关联。在rs3025039多态性的等位基因对比模型中按种族进行亚组分析后,我们发现亚洲人群的等位基因对比模型(T vs C:OR = 1.21,95%CI = 1.05 - 1.40,P = 0.007)存在显著关联。对于rs10434多态性,仅在纯合子模型(GG vs AA:OR = 0.75,95%CI = 0.57 - 0.98,P = 0.03)中观察到显著关联。对于rs1570360或rs2010963,在我们的研究中未观察到这两个多态性与RCC风险之间存在任何关联。

结论

我们的荟萃分析证实了rs699947、rs3025039和rs10434多态性与RCC风险升高显著相关这一事实。同时,本研究还表明rs3025039多态性的等位基因对比模型可能与亚洲人群的RCC风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb70/5367456/a74d38edccc8/ott-10-1725Fig1.jpg

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