PDF(Pubmed)
Abstract：
Angiogenesis is recognized as a hallmark of cancer, and vascular endothelial growth factor (VEGF) is a key regulator of the angiogenic process and is related to cancer progression. Anti-VEGF therapy has been tried but with limited success and without useful stratification for angiogenesis markers. Further, the landscape of VEGF single nucleotide polymorphisms (SNPs) in breast cancer and their clinical relevance is not well studied, and their relation to tissue-based angiogenesis markers has not been explored. Here, we studied a selection of VEGFA SNPs in nontumor lymph nodes from a population-based breast cancer cohort (n = 544), and their relation to clinicopathologic variables, vascular tissue metrics, and breast cancer-specific survival. Two of the SNP candidates (rs833068GA genotype and rs25648CC genotype) showed associations with angiogenesis tissue markers, and the VEGFA rs833068GA genotype was associated with breast cancer-specific survival among ER-negative cases. We also found trends of association between the rs699947CA genotype and large tumor diameter and ER-negative tumors, and between the rs3025039CC genotype and large tumor diameter. Our findings indicate some associations between certain VEGF SNPs, in particular the rs833068GA genotype, and both vascular metrics and patient survival. These findings and their potential implications need to be validated by independent studies.
摘要：
血管生成被认为是癌症的标志，血管内皮生长因子（VEGF）是血管生成过程的关键调节因子，与癌症进展有关。已经尝试了抗VEGF治疗,但成功有限,并且没有对血管生成标志物有用的分层。Further,VEGF单核苷酸多态性（SNPs）在乳腺癌中的应用前景及其临床相关性尚未得到很好的研究,它们与基于组织的血管生成标志物的关系尚未被研究。这里,我们从基于人群的乳腺癌队列（n=544）中研究了非肿瘤淋巴结中的VEGFASNP选择，以及它们与临床病理变量的关系，血管组织指标，和乳腺癌特异性生存率。其中两个SNP候选物（rs833068GA基因型和rs25648CC基因型）显示与血管生成组织标记相关，在ER阴性病例中，VEGFArs833068GA基因型与乳腺癌特异性生存率相关。我们还发现rs699947CA基因型与大肿瘤直径和ER阴性肿瘤之间的关联趋势。rs3025039CC基因型和大肿瘤直径之间。我们的发现表明某些VEGFSNP之间存在一些关联，特别是rs833068GA基因型，血管指标和患者生存率。这些发现及其潜在影响需要通过独立研究来验证。
