Telomere Length May Be Associated With Melanoma Risk

As most of you know, at the ends of chromosomes are stretches of DNA called telomeres. Each time a cell divides, it becomes shorter, losing the ability to further replicate. This shortening process is associated with not only aging and a higher risk of death, but with cancer as well.

Many cancers have shortened telomeres, such as bladder, bone, head and neck, kidney, lung, and pancreatic cancer. But when it comes to melanoma, researchers suggest that genes with longer telomere length may actually increase this risk.

Researcher Mark Iles, PhD, of the School of Medicine at the University of Leeds in the United Kingdom, and colleagues observed an interesting association between telomere score and melanoma.

In this genome melanoma study, seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11,108 case patients and 13,933 control patients from Australia, Europe, Israel, and the United States.

A genetic score was then formulated to help predict telomere length by determining the weighted mean of genotype dosage across the seven SNPs (the weights for each SNP were the age- and sex-adjusted estimates).

Researchers found a strong association between increased telomere score and increased risk of melanoma (P = 8.92×10⁻⁹) that was consistent across geographic regions. Categorizing telomere score into quartiles, they observed a linear effect on melanoma risk; those in the highest quartile are estimated to be at 1.29 times the risk of melanoma of those in the lowest quartile.

“For the first time, we have established that the genes controlling the length of these telomeres play a part in the risk of developing melanoma,” said Iles.

Previous studies have found a weak association between telomere-associated loci and disease risk. This statistically significant association confirms that the genetic factors underlying telomere length have an especially strong influence on melanoma risk and that, unusually, longer telomere length predisposes an individual to melanoma. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.

This also demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to environmental effects such as ultraviolet exposure or reverse causality.

“It will improve our understanding of melanoma biology and gives us a target toward developing potential treatments as well as potentially helping shape advice on what behavioral changes people might make," said Iles.

References:

• Healio: HemOnc Today. (2014). Genetic determinant identified for increased melanoma risk.