Publication Date:
2012-06-26
Description:
Tobacco smoke causes lung cancer in smokers and in never-smokers exposed to second-hand tobacco smoke (SHS). Nonetheless, molecular mechanisms of lung cancer in SHS-exposed never-smokers are still elusive. We studied lung cancers from current smokers ( n = 109), former smokers ( n = 56) and never-smokers ( n = 47) for promoter hypermethylation of five tumour suppressor genes— p16 , RARB , RASSF1 , MGMT and DAPK1 —using methylation-specific polymerase chain reaction. Lung tumours from ever-smokers suggested an increased risk of p16 hypermethylation as compared to never-smokers ( P = 0.073), with former smokers having the highest frequency of p16 hypermethylation ( P = 0.044 versus current smokers and P = 0.009 versus never-smokers). In the never-smoking group, p16 hypermethylation was seen in lung tumours from SHS-exposed individuals (4/33; 12%) but in none of the non-exposed individuals (0/9). The overall occurrence of hypermethylation (measured both as methylation index and as number of genes affected) was similar in those ever exposed to tobacco smoke (smokers, SHS-exposed never-smokers) and differed from non-exposed never-smokers. In multivariate analysis, p16 hypermethylation was more prevalent in lung tumours from male than female patients ( P = 0.018) and in squamous cell carcinomas than in adenocarcinomas ( P = 0.025). Occurrence of TP53 mutation in the tumour was associated with hypermethylation of at least one gene ( P = 0.027). In all, our data suggest that promoter hypermethylation pattern in SHS-exposed never-smokers resembles that observed in smokers. Association between TP53 mutation, a hallmark of smokers’ lung cancer, and methylation of one or more of the lung cancer-related genes studied, provides further evidence for common tobacco smoke-related origin for both types of molecular alterations.
Print ISSN:
0267-8357
Electronic ISSN:
1464-3804
Topics:
Biology
,
Medicine
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