November 04, 2014
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Genetic determinant identified for increased melanoma risk

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Genes associated with longer telomere length were linked to increased melanoma risk, according to study findings.

Moreover, the researchers noted that this association is not traceable to confounders, such as ultraviolet exposure or reverse causality.

“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,” researcher Mark Iles, PhD, of the School of Medicine at the University of Leeds in the United Kingdom, said in a press release.

In the genome-wide association study of melanoma, the researchers evaluated 11,108 case patients and 13,933 control patients from Europe, Israel, the United States and Australia. Based on data from a previous meta-analysis that identified seven single nucleotide polymorphisms associated with mean leukocyte telomere length, the researchers genotyped or well-imputed all seven SNPs in all melanoma genomic study samples.

For each sample, the researchers formulated a genetic score predicting telomere length by determining the weighted mean of genotype dosage across the seven relevant SNPs. The weight of each SNP was estimated using gender- and age-adjusted logistic ORs from the previous telomere meta-analysis. A logistic regression of melanoma risk was then generated using the genetic score.

Iles and colleagues observed a strong association between an increased telomere score and higher risk for melanoma (P=8.92 x 10-9) that persisted across geographic regions. After grouping telomere score into quartiles, the researchers found that patients in the highest quartile had 1.29 time increased risk of melanoma over those in the lowest quartile.

“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,” Iles said in the release. “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.”

Disclosure: Please see the full study for a list of relevant financial disclosures.