The Effect on Melanoma Risk of Genes Previously Associated With Telomere Length

نویسندگان

  • Mark M. Iles
  • D. Timothy Bishop
  • John C. Taylor
  • Nicholas K. Hayward
  • Myriam Brossard
  • Anne E. Cust
  • Alison M. Dunning
  • Jeffrey E. Lee
  • Eric K. Moses
  • Lars A. Akslen
  • Per A. Andresen
  • Marie-Françoise Avril
  • Esther Azizi
  • Giovanna Bianchi Scarrà
  • Kevin M. Brown
  • Tadeusz Dębniak
  • David E. Elder
  • Eitan Friedman
  • Paola Ghiorzo
  • Elizabeth M. Gillanders
  • Alisa M. Goldstein
  • Nelleke A. Gruis
  • Johan Hansson
  • Mark Harland
  • Per Helsing
  • Marko Hočevar
  • Veronica Höiom
  • Christian Ingvar
  • Peter A. Kanetsky
  • Maria Teresa Landi
  • Julie Lang
  • G. Mark Lathrop
  • Jan Lubiński
  • Rona M. Mackie
  • Nicholas G. Martin
  • Anders Molven
  • Grant W. Montgomery
  • Srdjan Novaković
  • Håkan Olsson
  • Susana Puig
  • Joan Anton Puig-Butille
  • Graham L. Radford-Smith
  • Juliette Randerson-Moor
  • Nienke van der Stoep
  • Remco van Doorn
  • David C. Whiteman
  • Stuart MacGregor
  • Karen A. Pooley
  • Sarah V. Ward
  • Graham J. Mann
  • Christopher I. Amos
  • Paul D. P. Pharoah
  • Florence Demenais
  • Matthew H. Law
  • Julia A. Newton Bishop
  • Jennifer H. Barrett
چکیده

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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عنوان ژورنال:

دوره 106  شماره 

صفحات  -

تاریخ انتشار 2014