Longer telomeres increase melanoma risk

Answer found in protective cap of chromosomes

A leading Dartmouth researcher, working with The Melanoma Genetics Consortium, GenoMEL, an international research consortium, co-authored a paper published today in the Journal of the National Cancer Institute that proves longer telomeres increase the risk of melanoma.

"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 lead author of the study Mark Iles, PhD, School of Medicine at the University of Leeds (UK).

Telomeres are a part of the genome that function like the plastic caps of your shoelaces, which prevent the laces from fraying. Instead they protect the ends of chromosomes from environmental damage, such as exposure to smoke or sunlight, which can harm them.

"Telomere length plays a key role in survival of cells and shorter telomere lengths are associated with aging and cardiovascular disease along with many cancers," said Christopher Amos, PhD, co-author and associate cancer center director for population sciences and interim deputy director at the Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, NH.

The GenoMEL study, conducted at the University of Leeds, looked at 11,108 melanoma cases and 13,933 control cases from Europe, Israel, United States, and Australia. It is the largest study to date to trace the genetic basis of telomere length in melanoma. It evaluated seven known or suspected genetic variations (also called SNPS) in a genome wide associate study (GWAS). It showed a strong association between telomere length and increased risk of melanoma.

"More research is needed to better understand the relationship between melanoma and telomeres, but learning more about how an individual's genetic telomere profile influences their risk developing melanoma may help us. It will improve our understanding of melanoma biology and gives us a target towards developing potential treatments as well as potentially helping shape advice on what behavioral changes people might make," said Iles.

The research team created a score representing genetically-determined telomere length, based on all the established telomere associated genes and found that this score was associated with melanoma risk. The one in four people predicted to have the longest telomeres are at 30 percent increased risk of developing melanoma compared to those one in four predicted to have the shortest telomeres.

The explanation for why a longer telomere is connected to melanoma is not yet known. Researchers propose that having a longer telomere may delay a cellular aging process, which increases the likelihood cellular variation.

"This research is important because it suggests that abnormal cell life span could play a key role in the development of melanomas and that agents targeting cell proliferation could be valuable for reducing melanoma growth," said Amos.