Correlation of 2,4-DDT with CDH1 Gene Promoter Methylation in Gastric Cancer

Ashrafi, Mohammad Reza; Asadi Karam, Gholamreza; Darvishmoghddam, Sadif; Abolhassani, Moslem; Iranpour, Maryam; Sepehri, Zahra

doi:10.34172/jkmu.2024.01

Document Type : Original Article

Authors

¹ Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

² Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran

³ Gastroenterology and Hepatology Research Center, Kerman University of Medical Sciences, Kerman, Iranersity of Sciences-Iran

⁴ Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

⁵ Pathology Department, Kerman faculty of medical science

⁶ Dept. of Biochemistry & Medical Genetics University of Manitoba

https://doi.org/10.34172/jkmu.2024.01

Abstract

Abstract
Background: Methylation alterations of tumor suppressor gene promoters are essential aspects of epigenetic changes in gastric cancer (GC). Cadherin1 (CDH1) encodes a protein with essential roles in cell-cell adhesions. In this study association of organochlorine pesticides (OCPs) serum levels with the methylation profile of this gene was investigated in gastric cancer (GC), intestinal metaplasia (IM), and functional dyspepsia (FD) patients.
Methods: GC (n=34), IM (n=8), and FD (n=48) patient serums were analyzed for the determination of OCP levels by gas chromatography equipment. The methylation status of the CDH1 gene promoter was examined by methylation-specific PCR (MSP) method. In order to confirm reduced protein expression of this gene in methylated samples, immunohistochemistry (IHC) was used.
Results: Our findings revealed significant hypermethylation of CDH1 gene promoter along with reduced expression in GC patients compared with IM and FD patients. Furthermore, there was significant association between CDH1 promoter hypermethylation and 2,4-DDT (odds ratio [OR]:1.183;95%CI:1.001-1.398, p=0.048) serum levels in GC patients.
Conclusion: Our results could suggest the association of 2,4-DDT OCP levels in the GC patient serums with CDH1 gene promoter hypermethylation. Additionally, this gene promoter methylation may play a role in the progression of pre-cancerous IM towards GC.

Highlights

Mohammad reza ashrafi(google scholar)(pubmed)

Gholamreza Asadi Karam(google scholar)(pubmed)

sadif darvishmoghddam(google scholar)(pubmed)

moslem abolhassani(google scholar)(pubmed)

maryam Iranpour(google scholar)(pubmed)

zahra sepehri(google scholar)(pubmed)

Keywords