Leal MF et al . Promoter hypermethylation in gastric cancer 2573 necessary to confirm this association. This is the first study that has evaluated the methylation status <strong>of</strong> CDH1, FHIT, MTAP and PLAGL1 promoters and their hypermethylation frequencies in gastric tissue samples in a population from Northern Brazil. The methylation status <strong>of</strong> MTAP promoter has never been investigated in gastric samples. Our findings show that hypermethylation is associated with gastric carcinogenesis. The H pylori infectious agent was present in 44.9% <strong>of</strong> samples and this infection may be a part <strong>of</strong> the carcinogenesis process through the gene promoter hypermethylation; especially the MTAP promoter in diffuse-type. Increased H pylori infection in diffuse-type may also be due to higher genetic predisposition. REFERENCES 1 Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. 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Cancer 2001; 91: 2294-2301 28 Zheng ZH, Sun XJ, Ma MC, Hao DM, Liu YH, Sun KL. Studies <strong>of</strong> promoter methylation status and protein expression <strong>of</strong> E-cadherin gene in associated progression stages <strong>of</strong> gastric cancer. Yichuan Xuebao 2003; 30: 103-108 29 Zazula M, Ferreira AM, Czopek JP, Kolodziejczyk P, Sinczak- Kuta A, Klimkowska A, Wojcik P, Okon K, Bialas M, Kulig J, Stachura J. CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion. Diagn Mol Pathol 2006; 15: 24-29 30 Waki T, Tamura G, Tsuchiya T, Sato K, Nishizuka S, Motoyama T. Promoter methylation status <strong>of</strong> E-cadherin, hMLH1, and p16 genes in nonneoplastic gastric epithelia. Am J Pathol 2002; 161: 399-403 31 Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, Hui WM, Rashid A, Kwong YL. 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2574 ISSN 1007-9327 CN 14-1219/R <strong>World</strong> J Gastroenterol May 14, 2007 Volume 13 Number <strong>18</strong> 35 Schildhaus HU, Krockel I, Lippert H, Malfertheiner P, Roessner A, Schneider-Stock R. Promoter hypermethylation <strong>of</strong> p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas <strong>of</strong> the esophagus, esophagogastric junction and proximal stomach. Int J Oncol 2005; 26: 1493-1500 36 Sozzi G, Pastorino U, Moiraghi L, Tagliabue E, Pezzella F, Ghirelli C, Tornielli S, Sard L, Huebner K, Pierotti MA, Croce CM, Pilotti S. Loss <strong>of</strong> FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res 1998; 58: 5032-5037 37 Berasain C, Hevia H, Fernandez-Irigoyen J, Larrea E, Caballeria J, Mato JM, Prieto J, Corrales FJ, Garcia-Trevijano ER, Avila MA. Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma. Biochim Biophys Acta 2004; 1690: 276-284 38 Furuta J, Umebayashi Y, Miyamoto K, Kikuchi K, Otsuka F, Sugimura T, Ushijima T. Promoter methylation pr<strong>of</strong>iling <strong>of</strong> 30 genes in human malignant melanoma. Cancer Sci 2004; 95: 962-968 39 Hellerbrand C, Muhlbauer M, Wallner S, Schuierer M, Behrmann I, Bataille F, Weiss T, Scholmerich J, Bosserh<strong>of</strong>f AK. Promoterhypermethylation is causing functional relevant downregulation <strong>of</strong> methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma. Carcinogenesis 2006; 27: 64-72 www.wjgnet.com 40 Wang Y, Yu Q, Cho AH, Rondeau G, Welsh J, Adamson E, Mercola D, McClelland M. Survey <strong>of</strong> differentially methylated promoters in prostate cancer cell lines. Neoplasia 2005; 7: 748-760 41 Abdollahi A. LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions. J Cell Physiol 2007; 210: 16-25 42 El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS. Interleukin-1 polymorphisms associated with increased risk <strong>of</strong> gastric cancer. Nature 2000; 404: 398-402 43 El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, Stanford JL, Mayne ST, Goedert J, Blot WJ, Fraumeni JF Jr, Chow WH. Increased risk <strong>of</strong> noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. <strong>Gastroenterology</strong> 2003; 124: 1193-1201 44 Hmadcha A, Bedoya FJ, Sobrino F, Pintado E. Methylationdependent gene silencing induced by interleukin 1beta via nitric oxide production. J Exp Med 1999; 190: 1595-1604 45 Vauhkonen M, Vauhkonen H, Sipponen P. Pathology and molecular biology <strong>of</strong> gastric cancer. Best Pract Res Clin Gastroenterol 2006; 20: 651-674 46 Yuasa Y. Control <strong>of</strong> gut differentiation and intestinal-type gastric carcinogenesis. Nat Rev Cancer 2003; 3: 592-600 S- Editor Liu Y L- Editor Roberts SE E- Editor Wang HF
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