Aberrant Gene Promoter Methylation in Sputum from Individuals Exposed to Smoky Coal Emissions

Background: Recent studies suggested the potential for aberrant gene promoter methylation in sputum as a predictive marker for lung cancer. Here, the promoter methylation of p16, MGMT, RASSF1A and DAPK genes was investigated in sputum of individuals exposed to smoky coal emissions in Xuan Wei, China, where the lung cancer rate is more than 6 times the Chinese national average. Materials and Methods: Sputum DNA of 107 noncancer individuals and 58 lung cancer patients was screened for promoter methylation using methylation-specific PCR. Results: Promoter methylation of the p16 gene was detected in about half (51.4% (55/107)) of sputum DNA from noncancer individuals, a frequency higher than that observed for the RASSF1A (29.9% ), MGMT (17.8% ) and DAPK (15.9% ) genes. Furthermore, the p16 gene was affected by promoter methylation at a frequency even higher among the lung cancer group, compared with the noncancer group (70.7% (41/58) versus 51.7% (55/107), p=0.017). Conclusion: Individuals exposed to smoky coal emissions in this region harbored frequent promoter methylation of these genes in their sputum and some of such alterations may be involved in lung tumor development. Aberrant promoter methylation of tumor suppressor genes is an important mechanism of gene transcriptional inactivation and has been associated with the development of many kinds of cancer (1), including lung cancer, the most common cause of cancer death worldwide. Although much attention has been paid to understanding the molecular and cellular mechanisms of lung cancer, the 5-year overall survival rate for all stages combined is only 15% (2), due primarily to the presence of