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

• Published in: JNCI : Journal of the National Cancer Institute Vol. 106; no. 10; p. 1
• Main Authors: ILES, Mark M, BISHOP, D. Timothy, ANDRESEN, Per A, AVRIL, Marie-Françoise, AZIZI, Esther, SCARRA, Giovanna Bianchi, BROWN, Kevin M, DEBNIAK, Tadeusz, ELDER, David E, FRIEDMAN, Eitan, GHIORZO, Paola, GILLANDERS, Elizabeth M, TAYLOR, John C, GOLDSTEIN, Alisa M, GRUIS, Nelleke A, HANSSON, Johan, HARLAND, Mark, HELSING, Per, HOCEVAR, Marko, HÖIOM, Veronica, INGVAR, Christian, KANETSKY, Peter A, LANDI, Mariateresa, HAYWARD, Nicholas K, LANG, Julie, LATHROP, G. Mark, LUBINSKI, Jan, MACKIE, Rona M, MARTIN, Nicholas G, MOLVEN, Anders, MONTGOMERY, Grant W, NOVAKOVIC, Srdjan, OLSSON, Håkan, PUIG, Susana, BROSSARD, Myriam, PUIG-BUTILLE, Joan Anton, RADFORD-SMITH, Graham L, RANDERSON-MOR, Juliette, VAN DER STOEP, Nienke, VAN DOORN, Remco, WHITEMAN, David C, MACGREGOR, Stuart, POOLEY, Karen A, WARD, Sarah V, MANN, Graham J, CUST, Anne E, AMOS, Christopher I, PHARAOH, Paul D. P, DEMENAIS, Florence, LAW, Matthew H, NEWTON BISHOP, Julia A, BARRETT, Jennifer H, DUNNING, Alison M, LEE, Jeffrey E, MOSES, Eric K, AKSLEN, Lars A
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.10.2014; Oxford Publishing Limited (England)
• Subjects: Australia; Biological and medical sciences; Brief Communication; Cancer and Oncology; Cancer och onkologi; Causality; Clinical Medicine; Confounding Factors, Epidemiologic; Dermatology; DNA Helicases - genetics; Effects; Europe; Germ-Line Mutation; Humans; Israel; Klinisk medicin; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Melanoma; Melanoma - genetics; Molecules; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Polymorphism; Polymorphism, Single Nucleotide; Predictive Value of Tests; Research Design; Ribonucleoproteins - genetics; Risk factors; RNA - genetics; Skin Neoplasms - genetics; Telomerase - genetics; Telomere - genetics; Telomere-Binding Proteins - genetics; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; United States; Zinc Fingers - genetics; Israel; Australia; United States; Europe; Association; Cancerology; Gene; Length; Risk factor; Malignant melanoma; Genetics; Risk; Malignant tumor; Telomere; Cancer
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/dju267

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.