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

Abstract

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.

Epigenetic silencing of BRCA1 gene associated with demographic and pathologic factors in sporadic breast cancer

“…Epigenetic changes play a major role in various genes that are potentially involved in human malignancies including breast cancer (BC) (Jones and Baylin, 2002;Widschwendter and Jones, 2002;Georgiou et al, 2007;Pandey et al, 2009). These changes involve the interplay between DNA methylation, histone modifications, and expression of noncoding RNAs in the regulation of gene transcription.…”

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

“…However, the relationship between gene-specific DNA methylation and smoking history/disease progression is not known (154). Georgiou et al reported methylation of the p16 promoter in sputum of patients with COPD that significantly correlated with heavy cigarette smoking, suggesting DNA methylation is associated with CS/oxidant-mediated lung diseases (45). Array-based methylation screening from two family-based cohorts (n = 1,085 and 396 subjects) revealed 349 CpG sites significantly associated with the presence and severity of COPD.…”

CpG Site–Specific Hypermethylation of p16INK4α in Peripheral Blood Lymphocytes of PAH-Exposed Workers

“…INK4a gene transcription activity (28,29,31) contained 389 bps (þ150 to þ538 bp around the transcription start site) and 35 CpG sites in total as illustrated in Fig. 1.…”