Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
Genes Genomics. 2022 Aug;44(8):923-936. doi: 10.1007/s13258-022-01269-2. Epub 2022 Jun 29.
Angiogenesis play a critical role in the development and progression of tumors in solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important endothelial cell mitogen which plays a critical role in normal physiological and tumor angiogenesis.
The objective of this case-control study was to investigate the association of VEGF-2578C/A, -2549 I/D, and -460T/C promoter polymorphisms with esophageal cancer risk in North-West Indians.
In this study, 200 sporadic esophageal cancer patients and 200 healthy, unrelated, age and gender matched controls were analyzed. The genomic DNA was extracted from blood samples using phenol chloroform method. Genotyping of VEGF- 2549I/D polymorphism was carried out by direct polymerase chain reaction (PCR) whereas VEGF -2578C/A and VEGF-460T/C) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
AA genotype (p = 0.005) and A allele (p = 0.005) VEGF -2578 C/A, II genotype (p = 0.011) and I allele (p = 0.012) of VEGF - 2549 I/D and CC genotype (p = 0.013) and C allele of VEGF-460T/C polymorphisms were significantly associated with increased risk of esophageal cancer. Stratification of data on the basis of gender showed that VEGF -2578 AA genotype (p = 0.001) and A allele (p = 0.001); VEGF -2549 II genotype (p = 0.002) and I allele (p = 0.002) and VEGF- 460CC genotype (p = 0.001) and C allele (p = 0.002) was significantly associated with increased risk of esophageal cancer in female group. Haplotype analysis revealed that A I C haplotype was significantly associated with increased risk for esophageal cancer in total samples (p = 0.008) as well as in female group (p = 0.001).
The results of present study indicate that VEGF -2578C/A, - 2549I/D and -460T/C polymorphisms were significantly associated with increased risk of esophageal cancer in North-West Indians.
血管生成在实体瘤的发展和进展中起着关键作用。血管内皮生长因子（VEGF）是最重要的内皮细胞有丝分裂原之一，在正常生理和肿瘤血管生成中起着关键作用。
本病例对照研究的目的是探讨血管内皮生长因子（VEGF）-2578C/A、-2549I/D 和-460T/C 启动子多态性与西北印度人群食管癌风险的关系。
本研究纳入 200 例散发性食管癌患者和 200 例年龄和性别相匹配的健康对照者。采用酚氯仿法从血样中提取基因组 DNA。采用直接聚合酶链反应（PCR）检测 VEGF-2549I/D 多态性，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测 VEGF-2578C/A 和 VEGF-460T/C 多态性。
AA 基因型（p=0.005）和 A 等位基因（p=0.005）VEGF-2578C/A、II 基因型（p=0.011）和 I 等位基因（p=0.012）VEGF-2549I/D 和 CC 基因型（p=0.013）和 VEGF-460T/C 多态性的 C 等位基因与食管癌风险增加显著相关。基于性别对数据进行分层显示，VEGF-2578AA 基因型（p=0.001）和 A 等位基因（p=0.001）；VEGF-2549II 基因型（p=0.002）和 I 等位基因（p=0.002）和 VEGF-460CC 基因型（p=0.001）和 C 等位基因（p=0.002）与女性组食管癌风险增加显著相关。单体型分析显示，A-I-C 单体型与总样本（p=0.008）和女性组（p=0.001）食管癌风险增加显著相关。
本研究结果表明，VEGF-2578C/A、-2549I/D 和-460T/C 多态性与西北印度人群食管癌风险增加显著相关。
