The effect on melanoma risk of genes previously associated with telomere length

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 Francoise Avril, Esther Azizi, Giovanna Bianchi Scarra, Kevin M. Brown, Tadeusz Dębniak, David E. Elder, Eitan Friedman, Paola Ghiorzo, Elizabeth M. GillandersAlisa M. Goldstein, Nelleke A. Gruis, Johan Hansson, Mark Harland, Per Helsing, Marko Hoçevar, Veronica Hoiom, 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 Novakovi, Hakan 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

    Research output: Contribution to journalArticle

    81 Scopus citations

    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 11 108 case patients and 13 933 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 = 8.92×10-9, 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.

    Original languageEnglish (US)
    Article numberdju267
    JournalJournal of the National Cancer Institute
    Volume106
    Issue number10
    DOIs
    StatePublished - Oct 1 2014

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Iles, M. M., Bishop, D. T., Taylor, J. C., Hayward, N. K., Brossard, M., Cust, A. E., Dunning, A. M., Lee, J. E., Moses, E. K., Akslen, L. A., Andresen, P. A., Avril, M. F., Azizi, E., Scarra, G. B., Brown, K. M., Dębniak, T., Elder, D. E., Friedman, E., Ghiorzo, P., ... Barrett, J. H. (2014). The effect on melanoma risk of genes previously associated with telomere length. Journal of the National Cancer Institute, 106(10), [dju267]. https://doi.org/10.1093/jnci/dju267