Mohammad reza ashrafi - Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Gholamreza Asadi Karam - Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran
sadif darvishmoghddam - Gastroenterology and Hepatology Research Center, Kerman University of Medical Sciences, Kerman, Iranersity of Sciences-Iran
moslem abolhassani - Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
maryam Iranpour - Pathology Department, Kerman faculty of medical science
zahra sepehri - Dept. of Biochemistry & Medical Genetics University of Manitoba

AbstractBackground: Methylation alterations of tumor suppressor gene promoters are essential aspects of epigenetic changes in gastric cancer (GC). Cadherin۱ (CDH۱) 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=۳۴), IM (n=۸), and FD (n=۴۸) patient serums were analyzed for the determination of OCP levels by gas chromatography equipment. The methylation status of the CDH۱ 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 CDH۱ gene promoter along with reduced expression in GC patients compared with IM and FD patients. Furthermore, there was significant association between CDH۱ promoter hypermethylation and ۲,۴-DDT (odds ratio [OR]:۱.۱۸۳;۹۵%CI:۱.۰۰۱-۱.۳۹۸, p=۰.۰۴۸) serum levels in GC patients.Conclusion: Our results could suggest the association of ۲,۴-DDT OCP levels in the GC patient serums with CDH۱ gene promoter hypermethylation. Additionally, this gene promoter methylation may play a role in the progression of pre-cancerous IM towards GC.

organochlorine pesticides, CDH۱, DNA methylation, Gastric cancer, intestinal metaplasia