Gene Variants Identified As Source of Deadly Illnesses

By Jane Farrell

Two widely carried gene variants that lead to longer chromosome caps also increase the risk of developing the brain cancers known as gliomas.

The researchers, led by scientists from the University of California, San Francisco, found that the variants lead to longer telomeres, the caps on chromosome ends that are thought to protect cells from aging.

The genetic variants, in two genes known as TERT and TERC, are respectively carried by 51 percent and 72 percent of the general population. Because the variants are so widespread, but the cancers that result are relatively rare, researchers believe that most of the time the telomeres are stronger than the increased risk of high-grade gliomas.

The research was published in Nature Genetics.

“There are clearly high barriers to developing gliomas, perhaps because the brain has special protection,” said Margaret Wrensch, MPH, PhD, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research at UCSF and senior author of the new study. “It’s not uncommon for people diagnosed with glioma to comment, ‘I’ve never been sick in my life.’”

The length of telomeres has both risks and benefits. In one British study, shorter telomeres were associated with an increased risk of heart disease. In much research, longer telomeres have been considered a sign of health – something that this newest research appears to contradict to some degree.

“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,” said lead author Kyle M. Walsh, PhD, assistant professor of neurological surgery at UCSF.

In the latest study, researchers from UCSF and The Mayo Clinic College of Medicine analyzed genome-wide data from 1,644 glioma patients and 7,736 healthy control. This work confirmed a link between TERT and gliomas and for the first time identified TERC as a glioma risk factor. The researchers also found that the TERC and TERC varians linked to glioma risk were also associated with greater telomere length.

Variants of TERT have also been linked to lung, prostate, testicular and breast cancers, and TERC variants to leukemia, colon cancer and multiple myeloma. Variants in both TERT and TERC have been found to increase risk of idiopathic pulmonary fibrosis, a progressive disease of the lungs.

In some of these cases, the disease-associated variants promote longer telomeres, and in others shorter telomeres, suggesting that “both longer and shorter telomere length may be pathogenic, depending on the disease under consideration,” the authors wrote.