Long telomere length increases the risk for lung adenocarcinoma

Long telomere length was associated with an increased risk for lung adenocarcinoma, according to a large study of 50,000 cases and 60,000 controls published online in Human Molecular Genetics.

"Our study adds genetic evidence to a growing body of literature that points to a causal association between long telomere length and lung adenocarcinoma," said study co-author Jennifer A. Doherty, PhD, an epidemiologist at the Norris Cotton Cancer Center at Dartmouth College's Geisel School of Medicine, in Lebanon, NH.

Telomeres, which cap off the ends of chromosomes and protect them from degradation and genomic instability, have been measured in prior studies by actual length. But such measurements can be prone to errors due to “wear and tear,” including biases from lifestyle or treatment-related factors.

In this study, researchers examined whether genetic factors that predict telomere length are involved in 5 of the most common cancers and their sub-types. They found that a genetic risk score for long telomere length was associated with increased risk of lung adenocarcinoma, but not for squamous cell lung cancer, prostate, breast, ovarian, or colorectal cancers.

"Of particular importance is our use of the Mendelian randomization approach, which has provided us with an important angle to examine telomere length without physically measuring it," explained the study’s corresponding author Brandon Pierce, PhD, assistant professor of epidemiology in the Department of Public Health Sciences at the University of Chicago, in Chicago, IL. "And this work provides compelling evidence that the traditional view that 'short telomeres are bad for health' does not hold for some cancer types—lung adenocarcinoma in particular."

Previous research had identified an association between long telomere length and increased risk for melanoma; the mechanism proposed for this is that long telomeres increase the proliferative duration of cells, which delays senescence and allows further mutations to occur.

“Future research efforts need to be undertaken to determine the value of telomeres as a novel risk measure or a modifiable pharmacological target, with the long-term goal of improving cancer prediction and prevention,” the authors concluded.

This study represents a large-scale collaboration through the GAME-ON network, which systematically combined data from 45 genome-wide association studies of various cancer types. These data are being used by a multidisciplinary group of researchers to examine many different hypotheses across cancer types.