title: 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.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, Box 357115, School of Medicine, University of Washington, Seattle, WA 98195-7115, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Salskov
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Stern
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
authors.forename: C Diana
authors.initials: CD
authors.lastname: Jordan
authors.forename: Linda
authors.initials: L
authors.lastname: Wiens
authors.forename: Janet
authors.initials: J
authors.lastname: Rasey
authors.forename: Hiep
authors.initials: H
authors.lastname: Lu
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
authors.forename: Hubert
authors.initials: H
authors.lastname: Vesselle