Are telomeres a double–edged sword?
The data obtained by researchers at the University of California at San Francisco, working under the guidance of Professor Margaret Wrensch, indicate that two common genetic variants associated with long telomeres significantly increase the risk of developing gliomas – brain tumors with a very unfavorable prognosis.
At the first stage of the work, the authors analyzed information on the genomes of 1,644 patients with glioma and 7,736 people in the control group. The data obtained confirmed the previously identified relationship between the risk of developing glioma and variations of the TERT gene, and also demonstrated for the first time that certain variations of the TERC gene are risk factors for the development of this disease.
It is known that both of these genes affect the activity of telomerase, an enzyme that restores telomeres, the end sections of chromosomes that shorten with each cell division and are considered a marker of biological age. To clarify the situation, the scientists added to the analyzed database information collected by researchers at the University of Leicester as part of a large-scale genomic analysis of telomere length. Almost 40,000 people participated in this study, and its results demonstrated the existence of a relationship between short telomeres and a high risk of developing cardiovascular diseases.
As a result, it was found that the variants of the TERT and TERC genes associated with the risk of developing glioma are also associated with a long telomere length.
The results of a large number of studies conducted in recent years indicate that long telomeres are a sign of good health. At the same time, the immortality of malignant cells is due to the maintenance of telomere length due to the activity of telomerase. Therefore, the developers of antitumor drugs are searching for compounds that can selectively block telomerase in tumor cells. This would lead to the death of malignant cells due to the accumulation of genetic damage.
Identified variants of the TERT and TERC genes are widespread and occur in 51% and 72% of people, respectively. Researchers believe that high cell viability, due to the long telomere length, generally neutralizes the risk of developing glioma, which is an inevitably fatal, but relatively rare type of cancer.
On the other hand, as the authors of the work note, the revealed pattern may extend not only to gliomas, since there is evidence that certain variants of the TERT gene are associated with the risk of lung, prostate, seminal and breast cancer, and variants of the TERC gene are associated with the risk of leukemia, colon cancer and myeloma diseases. A number of variants of both genes also increase the risk of developing idiopathic pulmonary fibrosis.
Disease-associated variants of these genes can cause both large and small telomere lengths. This indicates that, depending on the condition under consideration, both long and short telomeres may have a pathogenic character.
Article by Kyle M Walsh et al. Variations near TERT and TERC influencing telomere length are associated with high-grade glioma risk published in the journal Nature Genetics.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of California, San Francisco:
Longer Telomeres Linked to Risk of Brain Cancer.
10.06.2014