Aberrant p16 promoter methylation among Greek lung cancer patients and smokers:: correlation with smoking

Genetic and environmental factors (dietary and smoking) influence lung cancer epidemiology and induce epigenetic modifications that should be assessed in individual populations. We analyzed p16 methylation among Greek non-small cell lung carcinoma patients and smokers using two-stage methylation-specific polymerase chain reaction. One hundred and fifty specimens from cancerous and adjacent non-cancerous tissue, bronchial washings and sputum from patients and 48 specimens, mostly sputum, from disease-free smokers were included. p16 methylation was very frequent in biopsies (82.85%) and bronchial washings (non-small cell lung carcinoma, 80.35%; small cell lung carcinoma, 16.66%) from patients, but also in adjacent non-cancerous tissue (45.71%). Concordance of p16 methylation and positivity by cytological examination was 51.78%. Methylation was also observed in sputum from asymptomatic cytology-negative smokers (22.5%) and chronic obstructive pulmonary disease patients (three of eight). Among disease-free individuals, methylation correlated only with heavy smoking (> 50 pack-years, P < 0.001) and differed among male and female disease-free smokers. In summary, p16 methylation is very frequent among non-small cell lung carcinoma patients, and correlates with heavy cigarette consumption only in disease-free smokers.