An aberrant methylation in cancer-related genes is frequently detected in materials from gastric tumors, suggesting its involvement in the induction/promotion of gastric cancer [3–5]. The identification of methy-

DNA methylation is recognized as the most important epigenetic change in the malignant transformation. It includes global hypermethylation and the hypermethylation of CpG islands localized in the regulatory regions of most human genes [1, 2]. Methylated cytosine may undergo spontaneous deamination, producing a C → T transition, which, if in the promoter, may significantly affect the level of expression of a gene and eventually lead to its silencing. Methylated sequences in DNA are also targeted by specific proteins, which can recruit chromatin remodeling proteins changing the accessibility of a gene for transcription machinery and, again, affecting the level of its expression. An aberrant methylation in cancer-related genes is frequently detected in materials from gastric tumors, suggesting its involvement in the induction/promotion of gastric cancer [3–5]. The identification of methylated genes may provide an insight in the molecular mechanisms of tumor development and might reveal new tools to define markers of prognostic significance. In addition, identification of hypermethylated genes may be useful in cancer therapy, by more specific targeting cancer cells on the basis of their methylation status. To investigate the methylation pattern in gastric cancer we examined the methylation of the promoter of 8 tumor-suppressor genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1 and Fas. The products of these genes may protect the genome from mutagenesis (hMLH1, BRCA1, GSTP1, MDR1), impede deregulated progression through the cell cycle (BRCA1), induce apoptosis in cells that escape normal cell cycle controls (Apaf-1, Casp8, Fas), and inhibit cellular migration and metastasis (CDH1) [6]. The human Apaf-1 gene encodes a cytoplasmic protein involved in the mitochondrial apoptosis pathway [7]. The gene may be closely related to some protooncogenes and tumor suppressor genes, including p53 and Bcl-2 [8, 9]. The lowered expression of Apaf-1 gene or its inactivation was associated with methylation silencing in acute leukemia and laryngeal squamous carcinoma [10, 11]. The caspase 8 protein encoded by Casp8 gene plays also a major role in the process of apoptosis [7]. Because many anticancer drugs induce apoptosis by the activation of the caspase cascade, the deactivation of this pathway by silencing of Casp8 may lead to drug-resistance of cancer cells. The protein encoded by the Fas gene is a member of the family of death receptors that induce apoptosis in sensitive cells upon binding to their specific death ligands [12]. Silencing of the Fas receptor by DNA methylation was reported in several cancers [13]. The CDH1 gene encodes E-cadherin, a protein involved in cellular adhesion, tumor growth, invasion and metastasis [4, 14]. The hMLH1 gene encodes the DNA mismatch protein MLH1, playing a role in familial colorectal cancer and in sporadic gastric carcinomas that display microsatellite instability phenotype [3, 5, 15, 16]. BRCA1 is a breast cancer susceptibility protein, playing an essential role in the repair of DNA double strand breaks [17, 18]. The MDR1 gene codes for glycoprotein P, involved in cellular transport and its aberrant expression can be important for etiology and progression of various cancers [19]. GSTP1 is an enzyme, important for the detoxification of mutagens/carcinogens [20, 21]. In the present work we have also checked the association between the hypermethylation of and age, gender, smoking and family history of gastric cancer.