Association of Insertion/Deletion Polymorphisms of MDM2, MCP-1 and VEGF with Esophageal Cancer Risk in North-West Indians: A Case - Control Study

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

doi:10.31557/APJCP.2025.26.5.1623

Association of Insertion/Deletion Polymorphisms of MDM2, MCP-1 and VEGF with Esophageal Cancer Risk in North-West Indians: A Case - Control Study

Document Type : Research Articles

Authors

¹ Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India.

² Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.

³ Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.

10.31557/APJCP.2025.26.5.1623

Abstract

Background: The carcinogenesis process in esophageal cancer (EC), a highly heterogeneous and multifaceted disease, is influenced by both tumor angiogenesis and chronic inflammation pathways. Genetic variants in these pathways may affect the progression and development of EC, ultimately contributing to different susceptibilities to cancer among individuals. Methods: In this study, a total of 536 subjects were recruited, including 260 EC patients and 276 healthy individuals. The DNA was isolated from the blood samples of the participants using the standard phenol-chloroform method. The three insertion/deletion (ins/del) polymorphisms (VEGF-2549 18bp I/D, MDM2 40bp I/D, and MCP-1 14bp I/D) were screened using the Direct-polymerase chain reaction (PCR) genotyping method. The role of gene-environment interactions on EC risk was assessed using the Multifactor Dimensionality Reduction (MDR) software (version 3.0.2). Results: It was observed that the individuals carrying the II genotype and I allele of the VEGF-2549 18bp I/D polymorphism, as well as the carriers of the ID and DD genotypes and D allele of the MCP-1 14bp I/D polymorphism had a higher risk of developing EC. No association between the MDM2 40bp I/D polymorphism and EC risk was reported in this study. Genotype combination analysis revealed an increased EC risk in the carriers of the II-II-II genotype combination of the VEGF-2549 18bp I/D, MDM2 40bp I/D, and MCP-1 14bp I/D polymorphisms compared to those with other genotype combinations. The gene-environment interaction analysis also indicated a strong interaction between lifestyle factors and genetic polymorphisms in influencing EC risk. Conclusion: The present study concluded that the VEGF-2549 18bp I/D and MCP-1 14bp I/D variants were associated with EC risk in the North-west Indians.

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