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


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Authors

Iles, Mark M 
Bishop, D Timothy 
Taylor, John C 
Hayward, Nicholas K 
Brossard, Myriam 

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.

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Keywords

Australia, Confounding Factors, Epidemiologic, DNA Helicases, Europe, Germ-Line Mutation, Humans, Israel, Melanoma, Polymorphism, Single Nucleotide, Predictive Value of Tests, RNA, Research Design, Ribonucleoproteins, Skin Neoplasms, Telomerase, Telomere, Telomere-Binding Proteins, United States, Zinc Fingers

Journal Title

J Natl Cancer Inst

Conference Name

Journal ISSN

0027-8874
1460-2105

Volume Title

106

Publisher

Oxford University Press (OUP)
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (16565)
Isaac Newton Trust (1307 (k))