TY - JOUR
T1 - Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers
AU - Zöchbauer-Müller, Sabine
AU - Lam, Stephen
AU - Toyooka, Shinichi
AU - Virmani, Arvind K.
AU - Toyooka, Kiyomi O.
AU - Seidl, Sonja
AU - Minna, John D.
AU - Gazdar, Adi F.
PY - 2003/11/20
Y1 - 2003/11/20
N2 - 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 β-2 (RARβ-2), CDH13 (H-cadherin), p16INK4α (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) RARβ-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.
AB - 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 β-2 (RARβ-2), CDH13 (H-cadherin), p16INK4α (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) RARβ-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.
KW - Aberrant methylation
KW - Cigarette smoking
KW - Lung cancer
KW - Methylation-specific PCR
KW - Preneoplastic lesion
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U2 - 10.1002/ijc.11458
DO - 10.1002/ijc.11458
M3 - Article
C2 - 14520700
AN - SCOPUS:0142053910
SN - 0020-7136
VL - 107
SP - 612
EP - 616
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -