By Will Boggs MD
NEW YORK (Reuters Health) - Genetic variants that predispose individuals to longer telomere length appear to be associated with an increased risk of renal-cell carcinoma (RCC), according to results from a genome-wide association studies (GWAS) database analysis.
Recent studies have suggested that longer telomere length may be a risk factor for melanoma, lung cancer, chronic lymphocytic leukemia, glioma, and ovarian cancer, but studies of leukocyte telomere length and the risk of RCC have yielded inconsistent results.
Dr. Mark P. Purdue from the National Cancer Institute, Bethesda, Maryland, and colleagues used data from six RCC GWAS data sets, including 10,784 RCC cases and 20,406 controls of European ancestry, to examine the possible relationship between nine common single-nucleotide polymorphisms (SNPs) that are associated with longer telomere length and the risk of RCC.
The report was published online August 7 in European Urology.
Of the nine telomere length-associated SNPs, eight were associated with a significantly increased risk of RCC.
A genetic risk score based on the nine telomere length-associated variants predicted a doubling of RCC risk per kilobase increase in telomere length. Results were similar across RCC subtypes and after removing two variants that were in linkage disequilibrium with other known RCC susceptibility loci.
Patient sex, body-mass index, history of hypertension, and smoking status did not significantly modify these associations.
“Our investigation adds to the growing body of evidence indicating some aspect of telomere length is important for the development of a variety of common cancer types, suggesting clinicians weigh the potential increases in cancer risk when considering treatments with telomerase activating properties,” the researchers conclude in their report. “Future studies are needed to decipher which components of telomere biology, whether it be telomere length, telomerase activity, or an altogether unknown mechanism, are biologically important in oncogenesis. Such mechanistic insight will lead to improved risk modeling and identify potentially promising targets for drug development.”
Dr. Purdue did not respond to a request for comment by press time.
Eur Urol 2017.
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