Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer.
OBJECTIVE
The purpose of this study is to evaluate the usefulness of serum DNA methylation of five tumor suppressor genes for early detection of lung cancer.


METHODS
Methylation status in serum DNA from 200 patients undergoing bronchofiberscopic examination for abnormal findings on chest radiograph detected by lung cancer screening or surveillance was examined using methylation-specific PCR.


RESULTS
Ninety-one patients were given a pathologic diagnosis of lung cancer, 9 other malignant diseases, and 100 nonmalignant pulmonary diseases. In patients with lung cancer, methylation was detected in 18.7% for MGMT, 15.4% for p16(INK4a), 12.1% for RASSF1A, 11.0% for DAPK, and 6.6% for RAR-beta, which was higher compared with that in patients with nonmalignant diseases. Age and smoking status seemed to associate with methylation status. Sensitivity, specificity, and predictive value of methylation in at least one gene for diagnosis of lung cancer were 49.5%, 85.0%, and 75.0%, respectively. Adjusted odds ratio (95% confidence interval) for having lung cancer was 5.28 (2.39-11.7) for patients with methylation in one gene and 5.89 (1.53-22.7) for those with methylation in two or more genes. It is of note that methylation was identified in 50.9% of stage I lung cancer patients, whereas serum protein tumor markers were positive in 11.3% of them.


CONCLUSIONS
These results suggest that identification of promoter methylation of tumor suppressor genes in serum DNA could be useful for early detection of lung cancer.
Fujiwara
Keiichi
K
Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Fujimoto
Nobukazu
N
Tabata
Masahiro
M
Nishii
Kenji
K
Matsuo
Keitaro
K
Hotta
Katsuyuki
K
Kozuki
Toshiyuki
T
Aoe
Motoi
M
Kiura
Katsuyuki
K
Ueoka
Hiroshi
H
Tanimoto
Mitsune
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D016017:Odds Ratio; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; D019853:O(6)-Methylguanine-DNA Methyltransferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases