Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung

Abstract

It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39), CCND2 (21), CDH1 (7), and RARB (4) were hypermethylated in >2 of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26) than in never-smokers (3). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41) and never-smokers (30). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung. Copyright © 2011 Alexander Salskov et al.