Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.
Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Biochem Genet. 2024 Feb;62(1):547-573. doi: 10.1007/s10528-023-10419-4. Epub 2023 Jul 1.
Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR-RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a significant association between the VEGFA rs25648 C allele and breast cancer risk (OR 2.5, 95% CI 1.7-3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically significantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (p = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically significantly higher in breast cancer patients vs. control (p = 0.001). There was no significant difference in genotypes and allele frequencies of HIF1A rs11549465 polymorphism between breast cancer cases and control individuals (p > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (p < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a significant association with increased breast cancer risk in Egyptian patients.
乳腺癌是埃及女性中最常见的癌症类型。血管生成途径中的多态性先前与癌症风险和预后有关。本研究的目的是确定血管内皮生长因子 A (VEGFA)、血管内皮生长因子受体 2 (VEGFR2)、血管内皮生长抑制剂 (VEGI) 和缺氧诱导因子-1α (HIF1A) 基因中的某些多态性是否与乳腺癌的发生有关。该研究包括 154 名乳腺癌患者和 132 名年龄匹配的健康女性作为对照组。使用 (ARMS) PCR 技术对 VEGFA rs25648 进行基因分型；而 VEGFR2 rs2071559、VEGI rs6478106 和 HIF-1α rs11549465 则通过 PCR-RFLP 方法进行基因分型。通过 ELISA 测量乳腺癌患者和对照组中 VEGF、VEGFR2、VEGI 和 HIF1A 蛋白的血清水平。VEGFA rs25648 C 等位基因与乳腺癌风险之间存在显著关联（OR 2.5，95%CI 1.7-3.6，p<0.001）。与对照组相比，乳腺癌患者的 VEGFA rs25648 C/C 基因型显著更高（p<0.001）。与 C/C 基因型相比，具有 T/T 和 T/C VEGFR2 rs2071559 基因型的参与者患乳腺癌的几率分别高 5.46 倍和 5 倍。对于 VEGI rs6478106 多态性，乳腺癌患者的 C 等位基因比例高于对照组（p=0.003）。此外，与对照组相比，乳腺癌患者的 VEGI rs6478106 C/C 基因型显著更高（p=0.001）。乳腺癌病例与对照个体之间 HIF1A rs11549465 多态性的基因型和等位基因频率无显著差异（p>0.05）。与对照组相比，患有乳腺癌的女性的 VEGFA、VEGI 和 HIF1A 血清水平显著升高（p<0.001）。结论：在埃及患者中，VEGFA rs25648、VEGFR2 rs2071559 和 VEGI rs6478106 基因变异与乳腺癌风险增加显著相关。
