Impact of VEGFA promoter polymorphisms on esophageal cancer risk in North-West Indians: a case-control study

Kamlesh Guleria; Simranjot Kaur; Deepanshi Mahajan; Vasudha Sambyal; Meena Sudan; Manjit Singh Uppal

doi:10.1007/s13258-022-01269-2

Impact of VEGFA promoter polymorphisms on esophageal cancer risk in North-West Indians: a case-control study

Genes Genomics. 2022 Aug;44(8):923-936. doi: 10.1007/s13258-022-01269-2. Epub 2022 Jun 29.

Authors

Kamlesh Guleria¹, Simranjot Kaur², Deepanshi Mahajan², Vasudha Sambyal², Meena Sudan³, Manjit Singh Uppal⁴

Affiliations

¹ Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India. guleria_k@yahoo.com.
² Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
³ Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
⁴ Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.

PMID: 35767183
DOI: 10.1007/s13258-022-01269-2

Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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_-2578 I_{- 2549} C_{- 460} 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).

Conclusions: 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.

Keywords: Angiogenesis; Esophageal cancer; Polymorphism; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Esophageal Neoplasms* / genetics
Female
Genetic Predisposition to Disease
Humans
Polymorphism, Genetic
Vascular Endothelial Growth Factor A* / genetics

Substances

VEGFA protein, human
Vascular Endothelial Growth Factor A