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Home > Organization > Divisions and Independent Research Units > Group for Development of Molecular diagnostics and Individualized Therapy > Division of Epigenomics > Research Projects > Tobacco smoking and aberrant DNA methylation

Tobacco smoking and aberrant DNA methylation

Tobacco smoking is an important risk factor for lung, laryngeal, and esophageal cancers. As for the mechanism, carcinogenic chemicals in tobacco have been considered to be important. We found that aberrant DNA methylation of specific genes was accumulated in non-cancerous esophageal mucosa of patients with esophageal squamous cell carcinoma in association with smoking duration (Oka et al., 2009). It was suggested that esophageal squamous cell carcinomas develop from an epigenetic (and genetic) field for cancerization, which was produced due to tobacco smoking (Yamashita et al., 2018).

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Fig. Formation of an epigenetic field for cancerization by tobacco smoking

Aberrant DNA methylation accumulates by prolonged exposure to tobacco smoking, and forms an epigenetic field for cancerization. It was suggested that esophageal squamous cell carcinomas develop from such a field.

 

Esophageal cancer and DNA methylation

We identified 39 genes aberrantly methylated in esophageal squamous cell carcinomas (Oka et al., 2009 ). In five of the 39 genes, their methylation levels in non-cancerous esophageal mucosae had significant correlation with duration of tobacco smoking. On the other hand, regarding alcohol intake, another important risk factor, we did not observe any correlation (Oka et al., 2009 ). In many kinds of cancers, prolonged exposure to carcinogens and chronic inflammation are known to form a field defect for carcinogenesis by accumulation of aberrant DNA methylation. It was strongly suggested that an epigenetic field defect for esophageal squamous cell carcinomas is formed by prolonged exposure to tobacco smoking, and that esophageal squamous cell carcinomas develop from the epigenetic field. The epigenetic field defect will be a novel target not only for risk diagnosis but also for prevention of esophageal squamous cell carcinomas.

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Fig. Aberrant DNA methylation in non-cancerous esophageal mucosae

Aberrant DNA methylation is accumulated in non-cancerous esophageal mucosae. In five genes including MT1M, we found that methylation levels in non-cancerous esophageal mucosae had significant correlation with tobacco smoking duration.