Konac Ece, Onen H Ilke, Metindir Jale, Alp Ebru, Biri Aydan Asyali, Ekmekci Abdullah
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
DNA Cell Biol. 2007 Jul;26(7):453-63. doi: 10.1089/dna.2007.0585.
Tumor growth, which employs a number of regulators, requires the formation of new blood vessels. The most important regulators are vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). DNA sequence variations in VEGF and ANGPT-2 genes may lead to altered productions and/or activities of these genes. In this study, we aimed to determine the polymorphic effects of the changes in the VEGF -460 C/T, VEGF 936 C/T, and ANGPT-2 exon 4 G/A, which we perceive as risk factors in the progress and metastasis of cancer, on the gynecologic cancer patients in the Turkish population. Forty-seven ovarian, 32 cervical, and 21 endometrial cancer patients and 106 healthy controls were studied. The genomic DNA was extracted from the whole blood by using DNA extraction techniques. DNA samples were analyzed by polymerase chain reaction and restriction fragment length polymorphism. There were no significant differences between any of the three types of gynecologic cancer patients and controls in terms of the distribution of VEGF -460, VEGF 936, and ANGPT-2 genotypes and alleles (p > 0.05). Odds ratios (ORs) were calculated by logistic regression analysis in comparison with the most common homozygote genotype observed in the studied population. No evidence of a relationship that would constitute a risk factor (p > 0.05) was found between genotype and allele frequencies of patients and controls for VEGF -460, VEGF 936, and ANGPT-2 genes. A multivariable logistic regression analysis with the involvement of covariant factors, such as the history of gynecologic cancer and/or other cancer types in the family, stages of tumor, smoking habits, and existence of other diseases, did not change the results. The present study is the first case-control study of VEGF and ANGPT-2 polymorphisms in relation to ovarian, cervical, and endometrial cancers.
肿瘤生长需要形成新血管，这一过程受多种调节因子调控。其中最重要的调节因子是血管内皮生长因子（VEGF）和血管生成素-2（ANGPT-2）。VEGF和ANGPT-2基因的DNA序列变异可能导致这些基因的产生和/或活性发生改变。在本研究中，我们旨在确定VEGF -460 C/T、VEGF 936 C/T和ANGPT-2外显子4 G/A的变化（我们认为这些变化是癌症进展和转移的危险因素）对土耳其人群中妇科癌症患者的多态性影响。研究了47例卵巢癌、32例宫颈癌和21例子宫内膜癌患者以及106例健康对照。采用DNA提取技术从全血中提取基因组DNA。通过聚合酶链反应和限制性片段长度多态性分析DNA样本。在VEGF -460、VEGF 936和ANGPT-2基因型和等位基因分布方面，三种类型的妇科癌症患者与对照之间均无显著差异（p>0.05）。通过逻辑回归分析计算优势比（OR），并与研究人群中观察到的最常见纯合子基因型进行比较。在VEGF -460、VEGF 936和ANGPT-2基因的患者与对照的基因型和等位基因频率之间，未发现构成危险因素的关系证据（p>0.05）。纳入协变量因素（如妇科癌症病史和/或家族中其他癌症类型、肿瘤分期、吸烟习惯以及其他疾病的存在）的多变量逻辑回归分析并未改变结果。本研究是关于VEGF和ANGPT-2多态性与卵巢癌、宫颈癌和子宫内膜癌关系的首例病例对照研究。
