Quantification of free circulating DNA as a diagnostic marker in lung cancer.
OBJECTIVE
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.


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 in controls (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.


CONCLUSIONS
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.
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis; D016022:Case-Control Studies; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis / Q000097:blood*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000592:standards*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D019098:Telomerase