Short telomeres correlate with the risk of developing certain cancers. A new single-nucleotide polymorphism study finds long telomeres are associated with glioma risk. The work suggests glioma shares a common mechanism with colon cancer and multiple myeloma.

Long telomeres may protect against cardiovascular disease and promote longevity. They may also raise the risk of glioma, a new study in Nature Genetics reveals (Nat Genet 2014 June 8 [Epub ahead of print]).

In the popular view of telomeres, longer is better. Indeed, studies have linked truncated telomeres to reduced life span and increased vulnerability to heart disease and stroke. Research on the relationship between telomere length and cancer risk, however, has provided mixed results. For some cancers, including pancreatic and lung cancers, short telomeres correlate with greater susceptibility. For other cancer types, such as colon and breast, the opposite holds true.

Lead author Kyle Walsh, PhD, a genetic epidemiologist at the University of California, San Francisco, and colleagues weren't looking for a telomere connection when they began searching for new single-nucleotide polymorphisms (SNP) associated with glioma. The researchers first searched out SNPs in genotype data from 1,013 glioma patients and 6,595 healthy individuals. They then verified their findings by analyzing an additional 631 patients and 1,141 controls from independent sources. Most of the patients in both groups suffered from glioblastoma, the most common and most aggressive form of glioma.

The team found that a SNP with a large effect on glioma risk lies near the gene TERC, which encodes the RNA component of telomerase, the enzyme that lengthens telomeres. They also analyzed two previously identified SNPs that are located in the genes TERT and RTEL1, which encode proteins that spur telomere extension. Both SNPs showed a robust association with glioma risk.

To determine the relationship between these SNPs and telomere dimensions, the scientists turned to a 2013 genome-wide association study on leukocyte telomere length in more than 37,000 people of European ancestry. The SNP residing near TERC and the SNP in TERT showed a strong correlation with longer telomeres. In contrast, the SNP in RTEL1 was moderately associated with shorter telomeres.

The team also found that other glioma-linked genes, such as EGFR, didn't correlate with telomere length. That finding suggests there are multiple mechanisms for glioma development, not all of which involve telomeres.

“We have evidence that for glioma, longer telomeres are a risk factor or are a biomarker for risk,” says Walsh. However, researchers did not measure telomere length in glioma patients. If long telomeres do promote the development of glioma, how they accomplish it is unclear.

Walsh notes that TERT variants turn up in many kinds of cancer. However, researchers have uncovered cancer-associated variants of TERC only in colon cancer, multiple myeloma, and glioma. This similarity between disparate cancers suggests they have a common mechanism that might depend on telomere length, he says.

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