Scientists have recently completed a lengthy study in which over 200 people with premature aging disorders that are caused by unusually short telomeres were followed for 20 years. Telomeres are the protective caps that sit on the end of chromosomes and stop them from degrading; they get shorter each time a cell divides and are thought to have connections to aging and some diseases including cancer. Very short telomeres have also been associated with chromosome instability, and short telomere diseases have been linked to an increased risk of some types of cancer. This research has suggested, however, that in individuals with short telomere syndromes, chromosome instability is not causing that cancer risk increase. The findings have been reported in Cancer Cell.
In this study, the investigators suggested that the higher likelihood of cancer in patients with abnormally short telomeres is related to immune cells that age prematurely and die or disappear.
This work has highlighted the incredible importance of the immune system's duty to look for cancerous cells as we age, noted study co-author Mary Armanios, M.D., professor of oncology and director of the telomere center at the Johns Hopkins Kimmel Cancer Center, among other appointments.
Telomere syndromes are thought to be rare, but about half of people with a common type of pulmonary fibrosis also have short telomeres. People who carry telomeres that are at or lower than the 10th percentile of human telomere lengths have some premature aging characteristics; their hair tends to go gray when they are younger and their lungs scar at an earlier age than average.
In this study, the researchers tracked 226 patients with short telomere syndromes. Over the twenty-year course of the study, fifteen percent of patients, or 35 people got cancer. Most had blood cancers that have previously been linked to short telomeres. There were solid tumors in sixteen patients, and fourteen of these patients had squamous cancers that have been linked to immune suppression.
The genomes of cancer cells were sequenced for eight of these squamous cancer patients. The researchers could not find any evidence of chromosomal instability like fusions or swaps.
"In fact, these cancers seem to have less chromosomal instability than comparable squamous cancers that arise in people without short telomere syndromes," noted Armanios.
Twelve of the fourteen people with squamous cancer were found to have low T cell levels, however.
In a mouse model that carried short telomeres, this finding was confirmed; there were abnormally low levels of immune cells that fight cancer, and these mice could not effectively recruit T cells to the site of tumors.
This work may help clinicians identify patients who are at risk because they carry short telomeres, and help them avoid drugs that suppress the immune system.
Sources: Johns Hopkins University, Cancer Cell