Methylation and Polymorphism in CDH1 Gene Promoter Among Patients with Diffuse Gastric Cancer

Mohadeseh Naghi Vishteh; Mehrdad Zeinalian; Majid Kheirollahi; Amirreza Javadi Mamaghani; Mohammad Ali Zolfaghari; Aliyar Mirzapour; Meisam Barati; Seyed Javad Seyed Tabaei

doi:10.4103/ijpvm.IJPVM_288_20

Methylation and Polymorphism in CDH1 Gene Promoter Among Patients with Diffuse Gastric Cancer

Int J Prev Med. 2022 Mar 12:13:44. doi: 10.4103/ijpvm.IJPVM_288_20. eCollection 2022.

Authors

Mohadeseh Naghi Vishteh¹, Mehrdad Zeinalian¹, Majid Kheirollahi¹, Amirreza Javadi Mamaghani², Mohammad Ali Zolfaghari³, Aliyar Mirzapour⁴, Meisam Barati⁵, Seyed Javad Seyed Tabaei²

Affiliations

¹ Department of Genetics & Molecular biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
² Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Department of Parasitology and Mycology, School of Medcine Islamic Azad University Mashhad Branch, Mashhad, Iran.
⁵ Department of Cellular and Molecular Nutrition, Shahid Beheshti University of Medical, Tehran, Iran.

Abstract

Background: The promoter methylation and single nucleotide polymorphisms (SNPs) affect the transcription activity of cancer-related genes in several cancers including diffuse gastric cancer (DGC). Here we aimed to evaluate the promoter methylation status and the rs16260 at the promoter region of the CDH1 gene in DGC.

Methods: This case-control study was performed of 48 formalin-fixed paraffin-embedded (FFPE) blocks of DGC patients and 41 fresh frozen tissue samples of healthy individuals. Methylation status was evaluated using methylation-specific polymerase chain reaction (PCR) and the rs16260 at the promoter region of the CDH1 gene was assessed using PCR and sequencing method.

Results: The occurrence of methylation at the promoter region of the CDH1 gene in DGC patients was significantly higher than control samples (P < 0.0001). The methylated status was significantly associated with the poor differentiated histological type of DGC (P = 0.0428). The frequency of AC genotype and the A allele in DGC patients was significantly higher than the control subjects (P = 0.006 and 0.003, respectively).

Conclusions: Here we showed that methylation at the CDH1 promoter may contribute to the DGC development, and also the AC genotype was associated with the risk of DGC.

Keywords: Cadherin 1; methylation; polymerase chain reaction; sequence analysis; stomach neoplasms.