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About the Authors:
Mansour S. Al-Moundhri
* E-mail: [email protected]
Affiliation: Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University (SQU), Muscat, Sultanate of Oman
Maryam Al-Nabhani
Affiliation: Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University (SQU), Muscat, Sultanate of Oman
Letizia Tarantini
Affiliation: Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
Andrea Baccarelli
Affiliation: Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
Jennifer A. Rusiecki
Affiliation: Department of Preventive Medicine and Biometrics, Uniformed Services University, Bethesda, Maryland, United States of America
Introduction
Gastric cancer (GC) is a common malignancy that is a leading cause of cancer mortality worldwide [1]. GC has been linked to Helicobacter infection and environmental exposures including: smoking, salted fish, and low intake of fruit and vegetables [2], [3], . While these exposures are very common, very few exposed individuals develop GC. Therefore, it has been postulated that genetic factors such as single nucleotide polymorphisms in genes in several cellular pathways may increase GC risk [2], [3], [4], . In addition, studies have recently begun to elucidate the role of epigenetics, in particular DNA methylation, in GC initiation and progression [9], [10], [11]. Global DNA hypomethylation is associated with genomic instability, while DNA hypermethylation at CpG islands in or near gene promoter regions is associated with gene “silencing” [10], [12], [13]. Global genomic DNA methylation in cancerous gastric tissues has been found to be significantly lower than in non-cancerous tissues and shows a gradual increase in hypomethylation from normal gastric mucosa to chronic atrophic gastritis, severe, and intestinal metaplasia [10], [12], [13]. Global DNA hypomethylation occurs at an early stage in gastric carcinogenesis and may therefore serve as a novel biomarker of gastric neoplasia [12]. In contrast, several genes have been found to exhibit promoter hypermethylation resulting in gene silencing in GC. It has been suggested that the hypermethylation of the tumor suppressor genes, RUNX3 and TSLC1, may have value as molecular diagnostic markers, and hMLH1 and p16 methylation may predict stomach cancer risk...