Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer

• Published in: Journal of clinical oncology Vol. 21; no. 21; pp. 3902 - 3908
• Main Authors: Sozzi, Gabriella, Conte, Davide, Leon, MariaElena, Cirincione, Rosalia, Roz, Luca, Ratcliffe, Cathy, Roz, Elena, Cirenei, Nicola, Bellomi, Massimo, Pelosi, Giuseppe, Pierotti, Marco A., Pastorino, Ugo
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.11.2003; Lippincott Williams & Wilkins
• Subjects: Aged; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnosis; Case-Control Studies; DNA Primers; DNA, Neoplasm - analysis; DNA, Neoplasm - blood; DNA-Binding Proteins; Female; Humans; Logistic Models; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Male; Medical sciences; Middle Aged; Odds Ratio; Pneumology; Polymerase Chain Reaction - standards; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Telomerase - genetics; Tumors of the respiratory system and mediastinum; Human; Lung disease; Respiratory disease; Free form; Biological marker; Malignant tumor; non-small cell lung carcinoma; Blood plasma; DNA; Bronchus disease; Genetics; Diagnosis; Quantitative analysis
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.02.006

Purpose: Analysis of circulating DNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating DNA to identify patients with lung cancer and monitor their disease. Materials and Methods: The amount of plasma DNA was determined through the use of real-time quantitative polymerase chain reaction (PCR) amplification of the human telomerase reverse transcriptase gene (hTERT) in 100 non–small-cell lung cancer patients and 100 age-, sex-, and smoking-matched controls. Screening performance of the assay was calculated through the receiver operating characteristic (ROC) curve. Odds ratios were calculated using conditional logistic regression analysis. Results: Median concentration of circulating plasma DNA in patients was almost eight times the value detected incontrols (24.3 v 3.1 ng/mL). The area under the ROC curve was 0.94 (95% CI, 0.907 to 0.973). Plasma DNA was a strong risk factor for lung cancer; concentrations in the upper tertile were associated with an 85-fold higher risk than were those in the lowest tertile. Conclusion: This study shows that higher levels of free circulating DNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma DNA could also identify higher-risk individuals for lung cancer screening and chemoprevention trials.