{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:54:08Z","timestamp":1787961248309,"version":"build-2784847793"},"reference-count":36,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2004,6,15]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> The aim of this study was to identify tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer (NSCLC) by differentiating the age-related methylation from the tumor-specific methylation in NSCLC. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Eighty-five NSCLC patients and 127 cancer-free subjects participated in this study. Aberrant methylation at the promoters of the p16, Ras association domain family 1A (RASSF1A), fragile histidine triad (FHIT), H-cadherin, and retinoic acid receptor \u03b2 (RAR\u03b2) genes were evaluated in the resected tumor tissues and bronchial lavage samples of NSCLC patients and in the bronchial lavage samples of cancer-free subjects by methylation-specific polymerase chain reaction. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Of the 127 cancer-free samples, methylation was detected in 6% for p16, 13% for RAR\u03b2, 3% for H-cadherin, 4% for RASSF1A, and 28% for FHIT. Hypermethylation of the p16, RAR\u03b2, H-cadherin, and RASSF1A genes was not associated with patient age and smoking, whereas hypermethylation of the FHIT promoter occurred more frequently in older patients (P = .02) and was associated with exposure to tobacco smoke (P = .001). A strong correlation between age and smoking was found in patients with hypermethylation of the FHIT gene (r = 0.36; P = .03). A total of 68% of the bronchial lavage samples from the 85 NSCLC patients showed methylation of at least one of p16, RAR\u03b2, H-cadherin, and RASSF1A genes. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Our study suggests that tumor-specific methylation of the p16, RASSF1A, H-cadherin, and RAR\u03b2 genes may be a valuable biomarker for the early detection of NSCLC in bronchial lavage, and that the age-related methylation of FHIT gene in the normal bronchial epithelium is related to the exposure to tobacco smoke. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2004.10.077","type":"journal-article","created":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T18:03:07Z","timestamp":1087322587000},"page":"2363-2370","source":"Crossref","is-referenced-by-count":124,"title":["Tumor-Specific Methylation in Bronchial Lavage for the Early Detection of Non-Small-Cell Lung Cancer"],"prefix":"10.1200","volume":"22","author":[{"given":"Hojoong","family":"Kim","sequence":"first","affiliation":[{"name":"From the Division of Pulmonary and Critical Care Medicine, Department of Thoracic Surgery, and Department of Pathology, Samsung Medical Center, Sungkyunkwan University, School of Medicine; 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