Abstract

Background: Methylation alterations of tumor suppressor gene promoters are important epigenetic changes in gastric cancer. CDH1 encodes a protein (cadherin1) with essential roles in cell-cell adhesion. In this study, the association of organochlorine pesticide (OCP) serum levels with the methylation profile of this gene was investigated in gastric cancer, intestinal metaplasia (IM), and functional dyspepsia (FD) patients. Methods: Gastric cancer (n=34), IM (n=8), and FD (n=48) patient serums were analyzed for the determination of OCP levels by gas chromatography. The methylation status of the CDH1 gene promoter was examined by the methylation-specific PCR (MSP) method. Immunohistochemistry (IHC) was used to confirm the reduced protein expression of this gene in methylated samples. Results: Our findings revealed significant hypermethylation of the CDH1 gene promoter and its reduced expression in gastric cancer patients compared with IM and FD patients. Furthermore, there was a significant association between CDH1 promoter hypermethylation and 2,4-DDT (OR=1.183; 95% CI=1.001–1.398; P=0.048) serum levels in gastric cancer patients. Conclusion: Our results suggest an association between 2,4-DDT OCP levels in gastric cancer patient serums with CDH1 gene promoter hypermethylation. Additionally, this gene promoter’s methylation may play a role in the progression of pre-cancerous IM towards gastric cancer.