期刊
MUTAGENESIS
卷 27, 期 4, 页码 423-429出版社
OXFORD UNIV PRESS
DOI: 10.1093/mutage/ger092
关键词
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资金
- Finnish Cancer Foundation
- Yrjo Jahnsson Foundation [5447]
- Research Council of Lithuania [MIP-109]
- European Commission [EV5V-CT94-0555]
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.
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