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

J Clin Oncol. 2003 Nov 1;21(21):3902-8. doi: 10.1200/JCO.2003.02.006. Epub 2003 Sep 24.

Abstract

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 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.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • 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
  • Middle Aged
  • Odds Ratio
  • Polymerase Chain Reaction / standards*
  • Predictive Value of Tests
  • ROC Curve
  • Sensitivity and Specificity
  • Telomerase / genetics

Substances

  • DNA Primers
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Telomerase