Deoxyribonucleic Acid (DNA)methyltransferase Contributes To P16promoter CpG Island Methylation In Lung Adenocarcinoma With Smoking

Purpose:In this study,the relationship between Cp G island methylation and smoking and DNA methyltransferase in the occurrence and development of lung adenocarcinoma was explored by detecting p16 promoter methylation status.Method:Protein and m RNA levels of p16 were detected by immunohistochemistry and in situ hybridization assays.p16 gene promoter and exon 1 Cp G island locus Hap II sites methylation status was analyzed with the methylation-specific PCR.Results: Only 4 of 40 p16-positive cases were detected to methylate on CpG islands with10% methylating rate whereas 18 of p16-negative cases were methylated up to 36.73% of methylating rate.The methylating rates of both p16-positive and p16-negative groups were significantly different.17 of 50 cases with smoking from total 89 lung adenocarcinoma cases were detected to methylate on Cp G islands while only 5 of the remaining 39 non-smokers to methylate.The difference of the methylating rates in both smokers and non-smokers was significant to suggest the closely association of Cp G island methylation of p16 with smoking.Furthermore,p16 promoter Cp G islands were detected to methylate in 15 of 35 cases with higher DNA methyltransferase activity whereas only 7detected to methylate in the remaining 54 cases with lower DNA methyltransferase activity.Conclusions:p16 promoter Cp G island methylation likely made p16 expressing silence thus contributed to the tumorigenesis of lung adenocarcinoma.Smoking is likely to promote p16 Cp G island methylation or by its effect of the activity and metabolism of DNA methyltransferase 1(DNMT)on Cp G island methylation status.