The concentration of deoxyribonucleic acid in plasma from 73 patients with colorectal cancer and apparent clinical correlations
Introduction
The presence of high levels of cell-free DNA in plasma is not exclusive to cancer; it is also associated with, for example, infectious diseases (miliary tuberculosis and pyogenic abscess) [1], chronic inflammatory diseases (rheumatoid arthritis and systemic lupus erythematosus) [2], [3], tissue destruction (acute hepatitis, trauma and stroke), pregnancy, and treatment with high doses of corticoids [4].
There is a pressing need for clinical tools with which to make an early diagnosis and to detect the recurrence of tumors and to improve the monitoring of cancer patients. Many attempts have been made to develop routine laboratory tests [5] but, in colorectal cancer, for example, no definitive methods have been established [6], [7], [8], [9]. The quantitative techniques examined by different researchers include radioimmunoassay [10], [11], competitive PCR [11], [12], ELISA [11], [13], quantitative real-time PCR [8], [11], fluorometric quantitation [11], [14], and visual comparison with standards (DipStick Kits) [11], [15]. There is general agreement that, on average, levels of plasma DNA are elevated in cancer patients [5]. However, absolute amounts vary among studies, probably as a result of the different types of cancer studied and the great variety of techniques employed. Spectrophotometry has also been proved to be an useful tool for this for this purpose [11], [16], moreover, sophisticated and expensive procedures are normally not available in the clinical setting.
The aim of the present study was to quantify, by spectrophotometry, the cell-free DNA in plasma samples from patients with colorectal cancer at different stages of the disease and to attempt to correlate the resultant values with the clinical picture.
Section snippets
Patients
We reviewed the reports of 92 patients who had undergone resection of primary colorectal cancer in the Department of General Surgery at “La Paz” University Hospital (Madrid, Spain) between December 2002 and 2005. Tumors were at different stages and locations. We excluded 17 of these patients because their medical reports were incomplete and two because of acute inflammatory processes that were present with the cancer (peritumoral abscess and pancreatic pseudocyst, respectively). According to
Results
The mean plasma concentration (±S.D.) of DNA was 108 ± 156 ng/μl. The minimum value was 1 and the maximum was 812 ng/μl.
We did not find any association, in our series, between DNA concentration and the following parameters: age at the time of operation; gender; previous chemotherapy and radiotherapy; oncological records; tumor size; histological subtype of the tumor; differentiation grade; tumor localization; type of operation; local recurrence; and duration of storage of the sample.
Local
Discussion
The presence of extracellular nucleic acids (both DNA and RNA) in the bloodstream was first reported, in 1948, by Mandel and Métais, who detected both types, of nucleic acid in both healthy and diseased individuals [18]. Although their methods yielded inaccurate results, their basic finding was remarkable. However, it was not taken seriously. In the 1960s, Bendich et al. suggested that such cell-free DNA might be involved in the development of metastases [19]. Many years later, the neoplastic
Conflict of interest
None.
Acknowledgments
The authors thank Ms. Belen San Jose Valiente for her collaboration in the statistical analysis and Ms. Paloma Nebreda for her invaluable technical assistance during the course of this study.
This work was supported in part by a grant from “Fundación de Investigación Médica Mutua Madrileña (Spain)”.
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