The effect on melanoma risk of genes previously associated with telomere length
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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.
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Iles, M.; Bishop, D.; Taylor, J.; Hayward, N.; Brossard, M.; Cust, A.; Dunning, A.; Lee, J.; Moses, Eric; Akslen, L.; Andresen, P.; Avril, M.; Azizi, E.; Scarra, G.; Brown, K.; Debniak, T.; Elder, D.; Friedman, E.; Ghiorzo, P.; Gillanders, E.; Goldstein, A.; Gruis, N.; Hansson, J.; Harland, M.; Helsing, P.; Hoçevar, M.; Hoiom, V.; Ingvar, C.; Kanetsky, P.; Landi, M.; Lang, J.; Lathrop, G.; Lubinski, J.; Mackie, R.; Martin, N.; Molven, A.; Montgomery, G.; Novakovi, S.; Olsson, H.; Puig, S.; Puig-Butille, J.; Radford-Smith, G.; Randerson-Moor, J.; Van Der Stoep, N.; Van Doorn, R.; Whiteman, D.; Macgregor, S.; Pooley, K.; Ward, S.; Mann, G.; Amos, C.; Pharoah, P.; Demenais, F.; Law, M.; Bishop, J.; Barrett, J. (2014)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 ...
Zhang, J.; Rane, G.; Dai, X.; Shanmugam, M.; Arfuso, Frank; Samy, R.; Lai, M.; Kappei, D.; Kumar, Alan Prem; Sethi, G. (2016)© 2015 Elsevier B.V. Telomeres are the heterochromatic repeat regions at the ends of eukaryotic chromosomes, whose length is considered to be a determinant of biological ageing. Normal ageing itself is associated with ...
Coleman, M.; McHale, M.; Arnau, J.; Watson, A.; Oliver, Richard (1993)The molecular cloning of DNA from the telomere of one chromosome of Cladosporium fulvum, a fungal pathogen of tomato, is described. The telomeric DNA exhibits tandem repeats of the sequence TTAGGG running 5' to 3' toward ...