Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer
| Autor: | Kenji Sugio, Sabine Zöchbauer-Müller, Shinichi Toyooka, Adi F. Gazdar, John D. Minna, Michael Z. Gilcrease, Huei Lee, Dale McLerran, Kwun M. Fong, Kazunori Tsukuda, Kiyomi O. Toyooka, Chih Yi Chen, Riichiroh Maruyama, Arvind K. Virmani, Ziding Feng, Yasuro Fukuyama, Kenji Shimizu, Nobuyoshi Shimizu, Jack A. Roth |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Methyltransferase Tumor suppressor gene Receptors Retinoic Acid Adenomatous Polyposis Coli Protein Taiwan Biology Polymerase Chain Reaction O(6)-Methylguanine-DNA Methyltransferase GSTP1 Japan Risk Factors Carcinoma Non-Small-Cell Lung medicine Carcinoma Humans Genes Tumor Suppressor Promoter Regions Genetic Lung cancer Cyclin-Dependent Kinase Inhibitor p16 Aged Glutathione Transferase Aged 80 and over Tumor Suppressor Proteins Smoking Australia DNA Neoplasm Methylation DNA Methylation Middle Aged Cadherins medicine.disease United States Neoplasm Proteins respiratory tract diseases Isoenzymes Survival Rate Glutathione S-Transferase pi Oncology DNA methylation Cancer research Adenocarcinoma Female |
| Zdroj: | International Journal of Cancer. 103:153-160 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Aberrant methylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of lung cancers. There are major smoke exposure, histology, geography and gender-related changes in non-small cell lung cancer (NSCLC). We investigated smoking-related, histologic, geographic and gender differences in the methylation profiles of resected NSCLCs. We examined 514 cases of NSCLC and 84 corresponding nonmalignant lung tissues from 4 countries (USA, Australia, Japan and Taiwan) for the methylation status of 7 genes known to be frequently methylated in lung cancers [p16, RASSF1A (RAS association domain family 1), APC, RARbeta, CDH13, MGMT and GSTP1]. Multivariate analyses were used for data analysis. Adenocarcinoma was the major histologic type in women and never smokers; analyses that involved smoke exposure and gender were limited to this histology. Our major findings are a) methylation status of any single gene was largely independent of methylation status of other genes; b) the rates of methylation of p16 and APC and the mean Methylation Index (MI), a reflection of the overall methylation status, were significantly higher in ever smokers than in never smokers; c) the mean MI of tumors arising in former smokers was significantly lower than the mean of current smokers; d) the methylation rates of APC, CDH13 and RARbeta were significantly higher in adenocarcinomas than in squamous cell carcinomas; e) methylation rates of MGMT and GSTP1 were significantly higher in the USA and Australian cases than in those from Japan and Taiwan; and (f) no significant gender-related differences in methylation patterns were noted. Our findings demonstrate important smoke exposure, histologic type and geography-related differences in the methylation profiles of NSCLC tumors. |
| Databáze: | OpenAIRE |
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