Telomeres are the protective "caps" on the ends of chromosomes, and generally shorten as we age.
Credit: Chromosome illustration via Shutterstock
The same gene variants that are linked with having longer caps on chromosome tips and overall good health also may have a downside: They could increase the risk of brain cancer, a new study finds.
These new findings may be the first to suggest that people with longer telomeres — the protective stretches of DNA found at the ends of chromosomes — have an increased risk of cancer.
Past research had found that telomeres shorten as people age, causing scientists to speculate that increasing telomere length might protect cells from the effects of aging.
In addition, "shorter telomere length has previously been linked with cancer," said lead study author Kyle Walsh, a genetic epidemiologist at the University of California, San Francisco. "However, direct measurement of telomere length is complicated, because telomeres shorten with age, and cancer rates increase with age. As a result, the relationship between telomere length and cancer has previously been clouded by the effects of aging."
To get a closer look at the link between cancer and telomere length, Walsh and his colleagues focused on people with gliomas, the most common type of cancer of the central nervous system in adults. Gliomas are relatively rare but deadly — people with the most aggressive and common form of glioma — known as glioblastoma — typically survive for just 15 months following their diagnosis. [Extending Life: 7 Ways to Live Past 100]
The researchers analyzed the genomes of 1,644 glioma patients and the genomes of 7,736 healthy individuals. This work confirmed past research that had suggested a link between gliomas and a gene known as TERT, and also identified a gene known as TERC as a risk factor for glioma. Both TERT and TERC regulate the activity of telomerase, the enzyme that controls telomere length.
Further examination revealed that variants of both TERT and TERC that were associated with glioma risk were also linked to greater telomere length. About 51 percent of the general population carries the TERT genetic variant, and about 72 percent carries the TERC gene variant.
"Lengthened telomeres are generally considered to be a marker of healthy aging," Walsh told Live Science. "However, our data indicate they may simultaneously increase the risk of malignant brain tumors."
The researchers noted that although these variants do carry a higher risk of gliomas, they also may improve health overall by lengthening telomeres.
"It's not uncommon for people diagnosed with glioma to comment, 'I've never been sick in my life,'" senior study author Margaret Wrensch, of the University of California, San Francisco, said in a statement.
For instance, the scientists also found that shorter telomeres were associated with a significantly increased risk of heart disease, so longer telomeres may be a marker for a lower risk of heart disease.
"Though longer telomeres might be good for you as a whole person — reducing many health risks and slowing aging — they might also cause some cells to live longer than they're supposed to, which is one of the hallmarks of cancer," Walsh said in a statement.
Walsh noted that glioma is a relatively uncommon disease, "so even something that doubles risk still results in a very low lifetime risk of developing this cancer," Walsh said. In contrast, these newfound variants increase glioma risk by only 30 to 40 percent.
TERT variants are also linked to lung, prostate, testicular and breast cancers, and TERC variants are associated with leukemia, colon cancer and multiple myeloma (a cancer of white blood cells), Walsh added. Variants in both TERT and TERC have been found to increase the risk of a progressive disease of the lungs called idiopathic pulmonary fibrosis.
"A promising future line of investigation" will be to see whether these variants are linked with shorter or longer telomeres, Walsh said.
The scientists detailed their findings online June 8 in the journal Nature Genetics.