| Abstract [eng] |
Aberrant methylation in the promoter region of tumour suppressor genes (TSGs) is one of the mechanisms responsible for gene silencing during carcinogenesis. In lung cancer, p16, RASSF1A and RAR genes are frequently altered by hypermethylation in promoter region as a consequence of exposure to tobacco smoke. The main aim of our study was to optimize conditions for methylation specific PCR (MSP) and to analyze aberrant methylation in p16, RASSF1A and RAR genes in primary non-small cell lung carcinomas (NSCLC) from smokers and never-smokers. Aberrant methylation was analysed in 43 NSCLC from non-smokers and in 60 NSCLC from smokers, and relations to smoking status, histology, age and sex were evaluated. We found hypermethylation of p16 and RASSF1A genes to be frequent events in tobacco smoking patients. The rate of epigenetic alterations in p16 gene promoter was 33%, while RASSF1A gene was hypermethylated in 44% of tumour samples. Hypermethylation of p16 was more prevalent in squamous cell carcinomas (39%) than adenocarcinomas (18%), and in males (36%) than females (9%). There was no relationship between promoter hypermethylation and age. No significant differences in frequencies of hypermethylation were detected in NSCLC from never-smokers with and without documented exposure to environmental tobacco smoke. Analysis of epigenetic inactivation of tumour suppressor genes, particularly p16 and RASSF1A, may provide a valuable biomarker for lung cancer prevention in high-risk groups. |
