Radiation-induced lung adenocarcinoma is associated with increased frequency of genes inactivated by promoter hypermethylation.
Epigenetic inactivation of genes by promoter hypermethylation, a major mechanism in the initiation and progression of tobacco-induced cancer, has also been associated with lung cancer induced through environmental and occupational exposures. Our previous study of gene methylation in workers from the MAYAK nuclear enterprise identified a significantly higher prevalence for methylation of the p16 gene (CDKN2A) in adenocarcinomas from workers compared to tumors from non-worker controls. The purpose of this investigation was to determine whether genes in addition to p16 are "targeted" for silencing and whether overall gene methylation was more common in radiation-induced adenocarcinoma. A significant increase in the prevalence of methylation of GATA5 was seen in tumors from workers compared to tumors from controls. The prevalence for methylation of PAX5 beta and H-cadherin did not differ in tumors from workers and controls. Evaluating the frequency for methylation of a five-gene panel revealed that 93% of adenocarcinomas from workers compared to 66% of tumors from controls were methylated for at least one gene. Moreover, a twofold increase was seen in the number of tumors methylated for three or more genes for tumors from workers compared to controls. Increased frequency for inactivation of genes by promoter hypermethylation and targeting of tumor suppressor genes such as GATA5 may be factors that contribute to the increased risk for lung cancer associated with radiation exposure.
Lyon
Christopher M
CM
Lovelace Respiratory Research Institute, Lung Cancer Program, Albuquerque, New Mexico 87108, USA
Klinge
Donna M
DM
Liechty
Kieu C
KC
Gentry
Frederick D
FD
March
Thomas H
TH
Kang
Terri
T
Gilliland
Frank D
FD
Adamova
Galina
G
Rusinova
Galina
G
Telnov
Vitaliy
V
Belinsky
Steven A
SA
D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics; D004249:DNA Damage; D019175:DNA Methylation; D005260:Female; D050992:GATA5 Transcription Factor / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016273:Occupational Exposure / Q000009:adverse effects*; D051757:PAX5 Transcription Factor / Q000235:genetics; D011401:Promoter Regions, Genetic
D015820:Cadherins; D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; C099972:H-cadherin; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human