Telomere Length Indicates Cancer Risk

Researchers have found that the length of telomeres measured in white blood cells is indicative of the likelihood of an individual developing certain types of cancer.

Telomerase is the reverse transcriptase responsible for the extension of telomeric repeat sequences in most species studied. If telomerase activity is diminished or absent, telomeres will shorten. Shortened telomeres appear to lead to cell senescence. Eventually telomeric sequences can shorten to the point where they are not long enough to support the telomere-protein complex protecting the ends, and the chromosomes become unstable. These shortened ends become "'sticky” and promote chromosome rearrangements. Some rearrangements may contribute to the development of cancers.

Investigators at The University of Texas M. D. Anderson Cancer Center (Houston, USA; www.mdanderson.org) measured the length of the telomeres in white blood cells from patients participating in four ongoing studies of head and neck, bladder, lung, and renal cell cancers and from a group of healthy control subjects. Telomere length was measured using the Comet assay.

In the Comet assay, the cells are embedded in a thin agarose gel on a microscope slide. The cells are lysed to remove all cellular proteins and the DNA subsequently allowed unwinding under alkaline/neutral conditions. Following unwinding, the DNA is electrophoresed and stained with a fluorescent dye. During electrophoresis, broken DNA fragments (damaged DNA) or relaxed chromatin migrates away from the nucleus. The results published in the August 20, 2003, issue of the Journal of the National Cancer Institute showed that telomere lengths were significantly shorter in patients with all four types of cancers than they were in the control subjects.

The authors acknowledged that they measured telomere length in the easily obtainable white blood cells, not in cancer cells, and that cancer cells have different telomere dynamics. "Future research should focus on the associations of telomere dynamics, cell cycle checkpoints, apoptosis, the activation of telomerase, and DNA repair capacity, ultimately with the goal of enhancing our ability to identify high-risk subgroups,” they wrote.



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M. D. Anderson Cancer Center