1. The effect on melanoma risk of genes previously associated with telomere length.
- Author
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Iles MM, Bishop DT, Taylor JC, Hayward NK, Brossard M, Cust AE, Dunning AM, Lee JE, Moses EK, Akslen LA, Andresen PA, Avril MF, Azizi E, Scarrà GB, Brown KM, Dębniak T, Elder DE, Friedman E, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Harland M, Helsing P, Hočevar M, Höiom V, Ingvar C, Kanetsky PA, Landi MT, Lang J, Lathrop GM, Lubiński J, Mackie RM, Martin NG, Molven A, Montgomery GW, Novaković S, Olsson H, Puig S, Puig-Butille JA, Radford-Smith GL, Randerson-Moor J, van der Stoep N, van Doorn R, Whiteman DC, MacGregor S, Pooley KA, Ward SV, Mann GJ, Amos CI, Pharoah PD, Demenais F, Law MH, Newton Bishop JA, and Barrett JH
- Subjects
- Australia, Confounding Factors, Epidemiologic, DNA Helicases genetics, Europe, Humans, Israel, Predictive Value of Tests, RNA genetics, Research Design, Ribonucleoproteins genetics, Telomerase genetics, United States, Zinc Fingers genetics, Germ-Line Mutation, Melanoma genetics, Polymorphism, Single Nucleotide, Skin Neoplasms genetics, Telomere genetics, Telomere-Binding Proteins genetics
- Abstract
Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk., (© The Author 2014. Published by Oxford University Press.)
- Published
- 2014
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