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. Gillanders; Alisa 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

doi:10.1093/jnci/dju267

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

^*Corresponding author for this work

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Research output: Contribution to journal › Article › peer-review

104 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 language	English
Journal	Journal of the National Cancer Institute
Volume	106
Issue number	10
DOIs	https://doi.org/10.1093/jnci/dju267
State	Published - 1 Oct 2014

Funding

Funders	Funder number
National Institutes of Health
European Commission
National Cancer Institute	P30CA023108, P30CA016672, R01CA083115, P30CA016359
National Health and Medical Research Council	443036, 389891, 442915, 402761, 496610
Seventh Framework Programme	339462, 294576, 339446
Wellcome Trust	076113, 084766
Medical Research Council	MR/L01629X/1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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). https://doi.org/10.1093/jnci/dju267

@article{ce1e87ca679844979019d2ab2e4bf926,

title = "The effect on melanoma risk of genes previously associated with telomere length",

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.",

author = "Iles, \{Mark M.\} and Bishop, \{D. Timothy\} and Taylor, \{John C.\} and Hayward, \{Nicholas K.\} and Myriam Brossard and Cust, \{Anne E.\} and Dunning, \{Alison M.\} and Lee, \{Jeffrey E.\} and Moses, \{Eric K.\} and Akslen, \{Lars A.\} and Andresen, \{Per A.\} and Avril, \{Marie Francoise\} and Esther Azizi and Scarra, \{Giovanna Bianchi\} and Brown, \{Kevin M.\} and Tadeusz D{\c e}bniak and Elder, \{David E.\} and Eitan Friedman and Paola Ghiorzo and Gillanders, \{Elizabeth M.\} and Goldstein, \{Alisa M.\} and Gruis, \{Nelleke A.\} and Johan Hansson and Mark Harland and Per Helsing and Marko Ho{\c c}evar and Veronica Hoiom and Christian Ingvar and Kanetsky, \{Peter A.\} and Landi, \{Maria Teresa\} and Julie Lang and Lathrop, \{G. Mark\} and Jan Lubi{\'n}ski and Mackie, \{Rona M.\} and Martin, \{Nicholas G.\} and Anders Molven and Montgomery, \{Grant W.\} and Srdjan Novakovi and Hakan Olsson and Susana Puig and Puig-Butille, \{Joan Anton\} and Radford-Smith, \{Graham L.\} and Juliette Randerson-Moor and \{Van Der Stoep\}, Nienke and \{Van Doorn\}, Remco and Whiteman, \{David C.\} and Stuart Macgregor and Pooley, \{Karen A.\} and Ward, \{Sarah V.\} and Mann, \{Graham J.\} and Amos, \{Christopher I.\} and Pharoah, \{Paul D.P.\} and Florence Demenais and Law, \{Matthew H.\} and Bishop, \{Julia A.Newton\} and Barrett, \{Jennifer H.\}",

note = "Publisher Copyright: {\textcopyright} The Author 2014. Published by Oxford University Press.",

year = "2014",

month = oct,

day = "1",

doi = "10.1093/jnci/dju267",

language = "אנגלית",

volume = "106",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "10",

}

Iles, MM, Bishop, DT, Taylor, JC, Hayward, NK, Brossard, M, Cust, AE, Dunning, AM, Lee, JE, Moses, EK, Akslen, LA, Andresen, PA, Avril, MF, Azizi, E, Scarra, GB, Brown, KM, Dębniak, T, Elder, DE, Friedman, E, Ghiorzo, P, Gillanders, EM, Goldstein, AM, Gruis, NA, Hansson, J, Harland, M, Helsing, P, Hoçevar, M, Hoiom, V, Ingvar, C, Kanetsky, PA, Landi, MT, Lang, J, Lathrop, GM, Lubiński, J, Mackie, RM, Martin, NG, Molven, A, Montgomery, GW, Novakovi, S, Olsson, H, Puig, S, Puig-Butille, JA, Radford-Smith, GL, Randerson-Moor, J, Van Der Stoep, N, Van Doorn, R, Whiteman, DC, Macgregor, S, Pooley, KA, Ward, SV, Mann, GJ, Amos, CI, Pharoah, PDP, Demenais, F, Law, MH, Bishop, JAN & Barrett, JH 2014, 'The effect on melanoma risk of genes previously associated with telomere length', Journal of the National Cancer Institute, vol. 106, no. 10. https://doi.org/10.1093/jnci/dju267

TY - JOUR

T1 - The effect on melanoma risk of genes previously associated with telomere length

AU - Iles, Mark M.

AU - Bishop, D. Timothy

AU - Taylor, John C.

AU - Hayward, Nicholas K.

AU - Brossard, Myriam

AU - Cust, Anne E.

AU - Dunning, Alison M.

AU - Lee, Jeffrey E.

AU - Moses, Eric K.

AU - Akslen, Lars A.

AU - Andresen, Per A.

AU - Avril, Marie Francoise

AU - Azizi, Esther

AU - Scarra, Giovanna Bianchi

AU - Brown, Kevin M.

AU - Dębniak, Tadeusz

AU - Elder, David E.

AU - Friedman, Eitan

AU - Ghiorzo, Paola

AU - Gillanders, Elizabeth M.

AU - Goldstein, Alisa M.

AU - Gruis, Nelleke A.

AU - Hansson, Johan

AU - Harland, Mark

AU - Helsing, Per

AU - Hoçevar, Marko

AU - Hoiom, Veronica

AU - Ingvar, Christian

AU - Kanetsky, Peter A.

AU - Landi, Maria Teresa

AU - Lang, Julie

AU - Lathrop, G. Mark

AU - Lubiński, Jan

AU - Mackie, Rona M.

AU - Martin, Nicholas G.

AU - Molven, Anders

AU - Montgomery, Grant W.

AU - Novakovi, Srdjan

AU - Olsson, Hakan

AU - Puig, Susana

AU - Puig-Butille, Joan Anton

AU - Radford-Smith, Graham L.

AU - Randerson-Moor, Juliette

AU - Van Der Stoep, Nienke

AU - Van Doorn, Remco

AU - Whiteman, David C.

AU - Macgregor, Stuart

AU - Pooley, Karen A.

AU - Ward, Sarah V.

AU - Mann, Graham J.

AU - Amos, Christopher I.

AU - Pharoah, Paul D.P.

AU - Demenais, Florence

AU - Law, Matthew H.

AU - Bishop, Julia A.Newton

AU - Barrett, Jennifer H.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84930397756&partnerID=8YFLogxK

U2 - 10.1093/jnci/dju267

DO - 10.1093/jnci/dju267

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:84930397756

SN - 0027-8874

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 10

ER -

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

Abstract

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