International Journal of Preventive Medicine (Int J Prev Med)2008-78021332022041026372637ENDepartment of Genetics & Molecular biology, School of Medicine, Isfahan University of Medical Sciences, IsfahanDepartment of Genetics & Molecular biology, School of Medicine, Isfahan University of Medical Sciences, IsfahanDepartment of Genetics & Molecular biology, School of Medicine, Isfahan University of Medical Sciences, IsfahanDepartment of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, TehranDepartment of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, TabrizDepartment of Parasitology and Mycology, School of Medcine Islamic Azad University Mashhad Branch, MashhadDepartment of Cellular and Molecular Nutrition, Shahid Beheshti University of Medical, Tehran1 Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran20220410<strong>Background</strong>: 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. <strong>Methods</strong>: 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. <strong>Results</strong>: The occurrence of methylation at the promoter region of the CDH1 gene in DGC patients was significantly higher than control samples (P &lt; 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). <strong>Conclusions</strong>: 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.http://ijpm.mui.ac.ir/index.php/ijpm/article/view/2637http://ijpm.mui.ac.ir/index.php/ijpm/article/download/2637/717718478