Öz Gastric cancer (GC) is one of the most common types of cancer across the world. GC carcinogenesis demonstrates a multi-step progression with the accumulation of genetic and epigenetic changes. The genetic changes on gene expression, without any change on deoxyribonucleic acid (DNA) sequencing, are named as “epigenetic”. DNA methylation is the most commonly studied epigenetic modification in mammalians. Hypermethylation is observed on CpG (—C— phosphate—G—) islands In GC, promoter regions of genes. This is a significant mechanism that causes functional losses in tumor suppressor genes. In gastric cancer, DNA hypermethylation is seen in many genes. Helicobacter pylori (H. pylori) are a type of spiral-shaped Gram-negative bacteria. It infects approximately half of the world’s population. H. pylori is an important etiological factor that causes GC in human beings. Chronic H. pylori infection in human is associated with hypermethylation of promoter sequences of different genes. This paper provides a review of the current literature on the relationship between H. pylori infection and DNA hypermethylation in GC. J Microbiol Infect Dis 2015;5(4): 187-190Key words: Gastric cancer, Helicobacter pylori, DNA hypermethylation.
___
Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-2917.
Lauren P. The two histological main types of gastric carcinoma:
diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965;64:31-49
Yamamoto E, Suzuki H, Takamaru H, et al. Role of DNA ethylation
in the development of diffuse-type gastric cancer. Digestion 2011;83:241-249.
Dicken BJ, Bigam DL, Cass C, et al. Gastric adenocarcinoma:
review and considerations for future directions. Ann Surg 2005;241:27-39.
Shi J, Qu YP, Hou P. Pathogenetic mechanisms in gastric cancer.
World J Gastroenterol 2014;20:13804-13819.
Nakamura J,Tanaka T, Kitajima Y, et al. Methylation-mediated
gene silencing as biomarkers of gastric cancer: a review. World J Gastroenterol 2014;20:11991-2006.
Matsusaka K, Funata S, Fukayama M, Kaneda A. DNA methylation
in gastric cancer, related to Helicobacter pylori andEpstein-Barr virus. World J Gastroenterol 2014;20:3916-3926.
Qu Y, Dang S, Hou P. Gene methylation in gastric cancer. Clin
Chim Acta 2013;424:53-65.
Shin CM, Kim N, Jung Y, et al. Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci 2010; 101: 1337-1346.
Miyamoto K, Ushijima T. Diagnostic and therapeutic applications
of epigenetics. Jpn J Clin Oncol 2005;35:293-301.
Hu XT, He C. Recent progress in the study of methylated tumor suppressor genes in gastric cancer. Chin J Cancer 2013;32:31-41.
Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311-1315.
Amer AF, El-Sokkary RH, Elahmady M, et al. Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity. J Microbiol Infect Dis 2013;3:109-115.
Rhee KH, Park JS, Cho MJ. Helicobacter pylori: Bacterial Strategy for Incipient Stage and Persistent Colonization in Human Gastric Niches.Yonsei Med J 2014;55:1453-1466.
Alvarez MC, Santos JC, Maniezzo N, et al. GMT and MLH1
methylation in Helicobacter pylori-infected children and adults. World J Gastroenterol 2013;19:3043-3051.
Tatematsu M, Tsukamoto T, Mizoshita T. Role of Helicobacter
pylori in gastric carcinogenesis: the origin of gastric cancers and heterotopic proliferative glands in Mongolian gerbils. Helicobacter
;10:97-106.
Maekita T, Nakazawa K, Mihara M, et al. High levels of aberrant
DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 2006;12:989-995.
Chang WJ, Du Y, Zhao X, et al. Inflammation-related factors
predicting prognosis of gastric cancer.World J Gastroenterol
;20:4586-4596.
Arinton IG. Serum gastrin level and pepsinogen I/II ratio as
biomarker of Helicobacter pylori chronic gastritis. Acta Med Indones 2010;42:142-146.
Issa JP, Ahuja N, Toyota M, et al. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 2001;61:3573-3577.
Kondo Y, Kanai Y, Sakamoto M, et al. Genetic instability and
aberrant DNA methylation in chronic hepatitis and cirrhosis-
-A comprehensive study of loss of heterozygosity and microsatellite
instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology 2000;32:970-979.
Vasavi M, Ponnala S, Gujjari K, et al. DNA methylation in
esophageal diseases including cancer: special reference to hMLH1 gene promoter status. Tumori 2006;92:155-162.
Chan AO, Lam SK, Wong BC, et al. Promoter methylationof E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut 2003;52:502-506.
D’Elios MM, Manghetti M, De Carli M, et al. T helper 1 effector
cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol 1997;158:962-967.
Fu S, Ramanujam KS, Wong A, et al. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology
;116:1319-1329.
Niwa T, Tsukamoto T, Toyoda T, et al. Inflammatory processes
triggered by Helicobacter pylori infection cause aberrantDNA methylation in gastric epithelial cells. Cancer Res 2010;70:1430-1440.
Hur K, Niwa T, Toyoda T, et al. Insufficient role of cell roliferation
in aberrant DNA methylation induction and involvement of specific types of inflammation. Carcinogenesis 2011;32:35-41.
Yoshida T, Kato J, Maekita T, et al. Altered mucosal DNA methylation in parallel with highly active Helicobacter pylorirelated
gastritis. Gastric Cancer 2013;16:488-497.
Schneider BG, Peek RM Jr. Gastric cancer prevention by demethylation. Cancer Prev Res (Phila) 2013;6:253-256.
Niwa T, Toyoda T, Tsukamoto T, et al. Prevention of Helicobacter
pylori-induced gastric cancers in gerbils by a DNA demethylating
agent. Cancer Prev Res 2013;6:263-270.