p16INK4a and Histology-specific Methylation of CpG Islands by Exposure to Tobacco Smoke in Non-Small Cell Lung Cancer

摘要: The p16INK4a protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G1 phase cell cycle. Methylation CpG islands in promoter region is an important avenue for inactivation p16. mechanism methylation p16 region, however, has not been elucidated. Recent reports investigating non-small lung cancer (NSCLC) suggest that carcinogens tobacco smoke induce DNA process. We investigated association between and exposure to 185 primary NSCLCs. also studied relationship with mutation K-ras p53 genes, as well at DAP-kinase p14ARF loci. Finally, we evaluated prognostic significance NSCLC. prevalence was greater squamous carcinoma (41%) compared adenocarcinoma (22%; P = 0.03; Fisher’s exact test). significantly associated pack-years smoked (P 0.007; Wilcoxon rank sum test), duration smoking 0.0009; negatively time since quitting No nearby locus detected, either or smoke. In patients stage 1 adenocarcinoma, independent risk factor predicting shorter postsurgery survival 0.03), controlling significant effects other factors, including mutation. These findings tobacco-associated cancers occurs gene- tissue-specific manner induced directly indirectly by