Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
Department of Radiation Oncology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
Indian J Med Res. 2024 May;159(5):502-510. doi: 10.25259/ijmr_1862_22.
Background & objectives Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors which stimulates tumour progression induction of endothelial cell migration and division, inhibition of the apoptosis of endothelial cells, induction of serine protease activity and enhancement of vascular permeability. This study aimed to investigate the correlation of VEGF+405G/C,-7C/T and+936C/T polymorphisms with oesophageal cancer risk. Methods DNA samples of 464 subjects (231 sporadic oesophageal cancer affected individuals and 233 controls) were genotyped forVEGF+936C/T,+405G/C and-7C/T polymorphisms. VEGF+936C/T and +405G/C polymorphisms were genotyped by PCR-RFLP method whereas VEGF-7C/T polymorphism was genotyped using Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results CT genotype of VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer. VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer underdominant, co-dominant, over dominant and log-additive genetic models in total patients and in the female group. C+936G+405T-7 haplotype was significantly associated with decreased risk (P=0.01)of oesophageal cancer in total patients and also in the male group (P=0.02). Interpretation & conclusions In future, replication of the findings of the present study in a larger sample from different ethnic groups, along with functional analysis, may be insightful for the role of VEGFA polymorphisms in the pathogenesis of oesophageal cancer. Identification of the correlation of VEGF variants with specific therapy in oesophageal cancer may help in better selection of patients and monitoring treatment response in VEGF-therapy.
背景与目的 血管内皮生长因子（VEGF）是最重要的血管生成因子之一，可刺激肿瘤进展、诱导内皮细胞迁移和分裂、抑制内皮细胞凋亡、诱导丝氨酸蛋白酶活性和增强血管通透性。本研究旨在探讨 VEGF+405G/C、-7C/T 和+936C/T 多态性与食管癌风险的相关性。方法 对 464 例受试者（231 例散发性食管癌患者和 233 例对照）的 DNA 样本进行 VEGF+936C/T、+405G/C 和-7C/T 多态性检测。VEGF+936C/T 和+405G/C 多态性采用 PCR-RFLP 法检测，VEGF-7C/T 多态性采用扩增受阻突变系统-聚合酶链反应（ARMS-PCR）法检测。结果 VEGF-7C/T 多态性的 CT 基因型与食管癌发病风险降低显著相关。在总患者和女性组中，VEGF-7C/T 多态性在显性、共显性、超显性和对数相加遗传模型下均与食管癌发病风险降低显著相关。在总患者和男性组中，C+936G+405T-7 单倍型与食管癌发病风险降低显著相关（P=0.01；P=0.02）。结论 在未来，来自不同种族群体的更大样本的研究结果复制以及功能分析，可能有助于了解 VEGFA 多态性在食管癌发病机制中的作用。鉴定 VEGF 变体与食管癌特定治疗的相关性可能有助于更好地选择患者，并在 VEGF 治疗中监测治疗反应。
