Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual gene
Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers
✍ Scribed by Sabine Zöchbauer-Müller; Stephen Lam; Shinichi Toyooka; Arvind K. Virmani; Kiyomi O. Toyooka; Sonja Seidl; John D. Minna; Adi F. Gazdar
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 112 KB
- Volume
- 107
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor beta-2 (RARbeta-2), CDH13 (H-cadherin), p16(INK4a) (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RARbeta-2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens.
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## Abstract ## BACKGROUND The consumption of tobacco and alcohol has been implicated in the development of head and neck squamous cell carcinoma (HNSCC). Promoter methylation of tumor suppressor genes is common in HNSCC. In this study, the authors evaluated the effects of tobacco and alcohol on __