Molecular epidemiological study of oral cancer in Sri Lanka and Taiwan

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Oral squamous cell carcinoma and the most common oral premalignancies such as leukoplakia and oral submucous fibrosis appear to be related to the habit of betel quid chewing in South Asian countries including Sri Lanka and Taiwan. In this study, we carried out the molecular epidemiological analysis of oral cancer and related diseases to reveal the role of genetic and epigenetic backgrounds.We revealed the genetic changes such as p53 mutations and polymorphism CYP2A6, GSTM1, which could play an important role of carcinogenesis in the oral cancer. Especially, mutation of p53 gene was found out in the Exon 5 intensively and these phenomenon was not observed in the pre-cancerous lesions. These results strongly suggested that the one hit of the gene might not read the cancer lesion. DNA analysis of these patients indicated that polymorphisms of CYP2A6 (nitrosoamine activating enzyme) and GSTM1 (activated nitrosoamine metabolic enzyme) might be the candidates of the genetic background of the … More betel quid related diseases. Furthermore, epigenetic changes such as hypermethylation of tumor suppressor gene p15 and p16 and/or DNA repairing gene MGMT was investigated. In epithelial dysplasia and oral submucous fibrosis, the frequency of hypermethylation of p15 and p16 was significantly higher than those in normal epithelium. Betel quid chewing may cause p15 and p16 hypermethylation and metylation status of these genes was associated with epithelial dysplasia and their severity. This phenomenon was observed in the Japanese oral cancer, precancer lesions and also detected in the pathological normal tissues and the alcohol and /or smoking habit population frequently. Therefore, the hypermethylation of these genes may cause and associate with the oral cancer and disease development. Furthermore, these abnormalities of the DNA methylation status highly observed in the alcohol and /or smoking consumption population was possibly seemed to be one of the useful biomaker to evaluate the oral mucosa condition.In conclusion, these detections including genetic changes may be useful as not only a diagnostic tool for transformation and risk analysis, but also evaluating tool for the oral mucosal health conditions and prediction of the diseases. Less