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Clin Cancer Res ; 11(18): 6505-11, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16166426

RESUMO

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States, due in part to the lack of a validated and effective screening approach for early detection. The prevalence for methylation of seven and three genes was examined in DNA from sputum and plasma, respectively, from women at different risk for lung cancer. EXPERIMENTAL DESIGN: Lung cancer survivors (n = 56), clinically cancer-free smokers (n = 121), and never smokers (n = 74) comprised the study population. Plasma was collected from all three groups, whereas sputum was collected from lung cancer survivors and smokers. RESULTS: Methylation was detected in plasma DNA from 10 of 74 women who never smoked. Prevalence for methylation of the p16 gene in plasma was highest in lung cancer survivors. Lung cancer survivors showed a significant increase in the odds of having at least one or more genes methylated in plasma (odds ratio, 3.6; 95% confidence interval, 1.9-9.1) than never smokers. The prevalence for methylation of the O(6)-methylguanine-DNA methyltransferase, ras effector homologue 1, death associated protein kinase, and PAX5alpha genes in sputum was significantly higher in lung cancer survivors compared with smokers. Lung cancer survivors had 6.2-fold greater odds (95% confidence interval, 2.1-18.5) for methylation of three or more genes in sputum compared with smokers. Methylation was more commonly detected in sputum than plasma for O(6)-methylguanine-DNA methyltransferase and ras effector homologue 1, but not p16, in lung cancer survivors. CONCLUSION: Concomitant methylation of multiple gene promoters in sputum is strongly associated with lung cancer risk.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Proteínas de Ligação a DNA/genética , Proteínas Quinases Associadas com Morte Celular , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/genética , Fator de Transcrição PAX5 , Fatores de Risco , Fumar , Escarro/química , Escarro/citologia , Sobreviventes , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética
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