Longer telomeres linked to risk of brain cancer

June 8, 2014, University of California, San Francisco
Human chromosomes (grey) capped by telomeres (white). Credit: PD-NASA; PD-USGOV-NASA

New genomic research led by UC San Francisco (UCSF) scientists reveals that two common gene variants that lead to longer telomeres, the caps on chromosome ends thought by many scientists to confer health by protecting cells from aging, also significantly increase the risk of developing the deadly brain cancers known as gliomas.

The genetic variants, in two telomere-related genes known as TERT and TERC, are respectively carried by 51 percent and 72 percent of the general population. Because it is somewhat unusual for such risk-conferring variants to be carried by a majority of people, the researchers propose that in these carriers the overall cellular robustness afforded by longer telomeres trumps the increased risk of high-grade gliomas, which are invariably fatal but relatively rare cancers.

The research was published online in Nature Genetics on June 8, 2014.

"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.'"

In a possible example of this genetic balancing act between risks and benefits of telomere length, in one dataset employed in the current study—a massive genomic analysis of telomere length in nearly 40,000 individuals conducted at the University of Leicester in the United Kingdom—shorter telomeres were associated with a significantly increased risk of cardiovascular 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 ," said lead author Kyle M. Walsh, PhD, assistant professor of neurological surgery and a member of the Program in Cancer Genetics at UCSF's Helen Diller Family Comprehensive Cancer Center.

In the first phase of the new study, researchers at UCSF and The Mayo Clinic College of Medicine analyzed genome-wide data from 1,644 glioma patients and 7,736 healthy control individuals, including some who took part in The Cancer Genome Atlas project sponsored by the National Cancer Institute and National Human Genome Research Institute. This work confirmed a link between TERT and gliomas that had been made in previous UCSF research, and also identified TERC as a glioma risk factor for the first time.

Since both genes have known roles in regulating the action of telomerase, the enzyme that maintains telomere length, the research team combed the University of Leicester data, and they found that the same TERT and TERC variants associated with glioma risk were also associated with greater telomere length.

UCSF's Elizabeth Blackburn, PhD, shared the 2009 Nobel Prize in Physiology or Medicine for her pioneering work on telomeres and telomerase, an area of research she began in the mid-1970s. In the ensuing decades, untangling the relationships between telomere length and disease has proved to be complex.

In much research, longer telomeres have been considered a sign of health—for example, Blackburn and others have shown that individuals exposed to chronic stressful experiences have shortened telomeres. But because cancer cells promote their own longevity by maintaining telomere length, drug companies have searched for drugs to specifically target and block telomerase in tumors in the hopes that will accumulate genetic damage and die.

Walsh said the relevance of the new research should extend beyond gliomas, since TERT variants have also been implicated in lung, prostate, testicular and breast cancers, and TERC variants in 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 may be pathogenic, depending on the disease under consideration," the authors write.

Explore further: For older men, short telomeres can be a sign of chronic stress

More information: Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk, Nature Genetics, DOI: 10.1038/ng.3004

Related Stories

For older men, short telomeres can be a sign of chronic stress

March 11, 2014
(Medical Xpress)—Andrew Steptoe of University College London and his colleagues have found that telomere length can predict how long it takes older men to recover from stressful situations. Men with shorter telomeres have ...

Blood chromosome differences are linked to pancreatic cancer

October 23, 2012
A new study shows that a blood marker is linked to pancreatic cancer, according to a study published today by scientists at the University of Wisconsin Carbone Cancer Center and Mayo Clinic.

Lifestyle changes may lengthen telomeres, a measure of cell aging

September 16, 2013
A small pilot study shows for the first time that changes in diet, exercise, stress management and social support may result in longer telomeres, the parts of chromosomes that affect aging.

Newly discovered weakness in cancer cells make them more susceptible to chemotherapy

August 29, 2013
A new weakness has been discovered in cancer cells that may make them more susceptible to chemotherapy and other treatments. In a research report appearing in the September 2013 issue of The FASEB Journal, scientists identify ...

Link between faster 'biological' aging and risk of developing age-related diseases

March 27, 2013
An international team of scientists led by the University of Leicester has found new evidence that links faster 'biological' ageing to the risk of developing several age-related diseases - including heart disease, multiple ...

Recommended for you

Cholera spread tracked at household level

June 25, 2018
For the first time, the transmission of cholera has been tracked at the household level across Dhaka, Bangladesh, a city with a 'hyper-endemic' level of the disease. Researchers from the Wellcome Sanger Institute and their ...

Study identifies gene expression patterns associated with fatty liver disease

June 25, 2018
A fatty liver disease known as NASH—non-alcoholic steatohepatitis—is the nation's major cause of chronic liver disease, and is projected to become the most common indicator for liver transplants.

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

Deep data dive helps predict cerebral palsy

June 21, 2018
When University of Delaware molecular biologist Adam Marsh was studying the DNA of worms living in Antarctica's frigid seas to understand how the organisms managed to survive—and thrive—in the extremely harsh polar environment, ...

Genetic variation in progesterone receptor tied to prematurity risk, study finds

June 21, 2018
Humans have unexpectedly high genetic variation in the receptor for a key pregnancy-maintaining hormone, according to research led by scientists at the Stanford University School of Medicine. The finding may help explain ...

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.