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Effects of dietary intake and genetic factors on hypermethyiation of the hMLH1 gene promoter in gastric cancer

World Journal of Gastroenterology 2005年第25期11卷 3834-3841页

作者： Young-Jin Song Hyo-Yung Yun Joo-Seung Park Heon Kim Departments of Surgery Department of Surgery Department of Preventive Medicine

AIM: Hypermethylation of the promoter of the hMLH1gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric ***: Data were obtained from a hospital-based,case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk *** of the hMLH1 gene promoter,polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were ***: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2, and L-mycgenes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 *** of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation,whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter *** of the hMLH1 gene promoter was significantly inversely correlated with mutation of the ***: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, G

关键词： Gastric cancer Environmental carcinogens Genetic polymorphisms hmtlh1 Microsatellite instability p53 Ki-ras

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