Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

T. Rafnar; P. Sulem; S.N. Stacey; F. Geller; J. Gudmundsson; A. Sigurdsson; M. Jakobsdottir; H. Helgadottir; S. Thorlacius; K.K. Aben; T. Blondal; T.E. Thorgeirsson; G. Thorleifsson; K. Kristjansson; K. Thorisdottir; R. Ragnarsson; B. Sigurgeirsson; H. Skuladottir; T. Gudbjartsson; H.J. Isaksson; G.V. Einarsson; K.R. Benediktsdottir; B.A. Agnarsson; K. Olafsson; A. Salvarsdottir; H. Bjarnason; M. Asgeirsdottir; K.T. Kristinsson; S. Matthiasdottir; S.G. Sveinsdottir; S. Polidoro; V. Hoiom; R. Botella Estrada; K. Hemminki; P. Rudnai; D.T. Bishop; M. Campagna; E. Kellen; M.P. Zeegers; P. de Verdier; A. Ferrer; D. Isla; M.J. Vidal; R. Andres; B. Saez; P. Juberias; J. Banzo; S. Navarrete; A. Tres; D. Kan; A. Lindblom; E. Gurzau; K. Koppova; F. van de Vegt; J.A. Schalken; H.F. van der Heijden; H.J. Smit; R.A. Termeer; E. Oosterwijk; O. van Hooij; E. Nagore; S. Porru; G. Steineck; J. Hansson; F. Buntinx; W.J. Catalona; G. Matullo; P. Vineis; A.E. Kiltie; J.I. Mayordomo; R. Kumar; L.A. Kiemeney; M.L. Frigge; T. Jonsson; H. Saemundsson; R.B. Barkardottir; E. Jonsson; S. Jonsson; J.H. Olafsson; J.R. Gulcher; G. Masson; D.F. Gudbjartsson; A. Kong; U. Thorsteinsdottir; K. Stefansson

doi:10.1038/ng.296

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

T. Rafnar^*, P. Sulem, S.N. Stacey, F. Geller, J. Gudmundsson, A. Sigurdsson, M. Jakobsdottir, H. Helgadottir, S. Thorlacius, K.K. Aben, T. Blondal, T.E. Thorgeirsson, G. Thorleifsson, K. Kristjansson, K. Thorisdottir, R. Ragnarsson, B. Sigurgeirsson, H. Skuladottir, T. Gudbjartsson, H.J. IsakssonG.V. Einarsson, K.R. Benediktsdottir, B.A. Agnarsson, K. Olafsson, A. Salvarsdottir, H. Bjarnason, M. Asgeirsdottir, K.T. Kristinsson, S. Matthiasdottir, S.G. Sveinsdottir, S. Polidoro, V. Hoiom, R. Botella Estrada, K. Hemminki, P. Rudnai, D.T. Bishop, M. Campagna, E. Kellen, M.P. Zeegers, P. de Verdier, A. Ferrer, D. Isla, M.J. Vidal, R. Andres, B. Saez, P. Juberias, J. Banzo, S. Navarrete, A. Tres, D. Kan, A. Lindblom, E. Gurzau, K. Koppova, F. van de Vegt, J.A. Schalken, H.F. van der Heijden, H.J. Smit, R.A. Termeer, E. Oosterwijk, O. van Hooij, E. Nagore, S. Porru, G. Steineck, J. Hansson, F. Buntinx, W.J. Catalona, G. Matullo, P. Vineis, A.E. Kiltie, J.I. Mayordomo, R. Kumar, L.A. Kiemeney, M.L. Frigge, T. Jonsson, H. Saemundsson, R.B. Barkardottir, E. Jonsson, S. Jonsson, J.H. Olafsson, J.R. Gulcher, G. Masson, D.F. Gudbjartsson, A. Kong, U. Thorsteinsdottir, K. Stefansson

^*Corresponding author for this work

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

Abstract

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

Original language	English
Pages (from-to)	221-7
Journal	Nature Genetics
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/ng.296
Publication status	Published - 1 Jan 2009

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Rafnar, T., Sulem, P., Stacey, S. N., Geller, F., Gudmundsson, J., Sigurdsson, A., Jakobsdottir, M., Helgadottir, H., Thorlacius, S., Aben, K. K., Blondal, T., Thorgeirsson, T. E., Thorleifsson, G., Kristjansson, K., Thorisdottir, K., Ragnarsson, R., Sigurgeirsson, B., Skuladottir, H., Gudbjartsson, T., ... Stefansson, K. (2009). Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nature Genetics, 41(2), 221-7. https://doi.org/10.1038/ng.296

Rafnar, T. ; Sulem, P. ; Stacey, S.N. ; Geller, F. ; Gudmundsson, J. ; Sigurdsson, A. ; Jakobsdottir, M. ; Helgadottir, H. ; Thorlacius, S. ; Aben, K.K. ; Blondal, T. ; Thorgeirsson, T.E. ; Thorleifsson, G. ; Kristjansson, K. ; Thorisdottir, K. ; Ragnarsson, R. ; Sigurgeirsson, B. ; Skuladottir, H. ; Gudbjartsson, T. ; Isaksson, H.J. ; Einarsson, G.V. ; Benediktsdottir, K.R. ; Agnarsson, B.A. ; Olafsson, K. ; Salvarsdottir, A. ; Bjarnason, H. ; Asgeirsdottir, M. ; Kristinsson, K.T. ; Matthiasdottir, S. ; Sveinsdottir, S.G. ; Polidoro, S. ; Hoiom, V. ; Botella Estrada, R. ; Hemminki, K. ; Rudnai, P. ; Bishop, D.T. ; Campagna, M. ; Kellen, E. ; Zeegers, M.P. ; de Verdier, P. ; Ferrer, A. ; Isla, D. ; Vidal, M.J. ; Andres, R. ; Saez, B. ; Juberias, P. ; Banzo, J. ; Navarrete, S. ; Tres, A. ; Kan, D. ; Lindblom, A. ; Gurzau, E. ; Koppova, K. ; van de Vegt, F. ; Schalken, J.A. ; van der Heijden, H.F. ; Smit, H.J. ; Termeer, R.A. ; Oosterwijk, E. ; van Hooij, O. ; Nagore, E. ; Porru, S. ; Steineck, G. ; Hansson, J. ; Buntinx, F. ; Catalona, W.J. ; Matullo, G. ; Vineis, P. ; Kiltie, A.E. ; Mayordomo, J.I. ; Kumar, R. ; Kiemeney, L.A. ; Frigge, M.L. ; Jonsson, T. ; Saemundsson, H. ; Barkardottir, R.B. ; Jonsson, E. ; Jonsson, S. ; Olafsson, J.H. ; Gulcher, J.R. ; Masson, G. ; Gudbjartsson, D.F. ; Kong, A. ; Thorsteinsdottir, U. ; Stefansson, K. / Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. In: Nature Genetics. 2009 ; Vol. 41, No. 2. pp. 221-7.

@article{1e292bd3607d4936a85d50f8d5b34594,

title = "Sequence variants at the TERT-CLPTM1L locus associate with many cancer types",

abstract = "The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.",

author = "T. Rafnar and P. Sulem and S.N. Stacey and F. Geller and J. Gudmundsson and A. Sigurdsson and M. Jakobsdottir and H. Helgadottir and S. Thorlacius and K.K. Aben and T. Blondal and T.E. Thorgeirsson and G. Thorleifsson and K. Kristjansson and K. Thorisdottir and R. Ragnarsson and B. Sigurgeirsson and H. Skuladottir and T. Gudbjartsson and H.J. Isaksson and G.V. Einarsson and K.R. Benediktsdottir and B.A. Agnarsson and K. Olafsson and A. Salvarsdottir and H. Bjarnason and M. Asgeirsdottir and K.T. Kristinsson and S. Matthiasdottir and S.G. Sveinsdottir and S. Polidoro and V. Hoiom and {Botella Estrada}, R. and K. Hemminki and P. Rudnai and D.T. Bishop and M. Campagna and E. Kellen and M.P. Zeegers and {de Verdier}, P. and A. Ferrer and D. Isla and M.J. Vidal and R. Andres and B. Saez and P. Juberias and J. Banzo and S. Navarrete and A. Tres and D. Kan and A. Lindblom and E. Gurzau and K. Koppova and {van de Vegt}, F. and J.A. Schalken and {van der Heijden}, H.F. and H.J. Smit and R.A. Termeer and E. Oosterwijk and {van Hooij}, O. and E. Nagore and S. Porru and G. Steineck and J. Hansson and F. Buntinx and W.J. Catalona and G. Matullo and P. Vineis and A.E. Kiltie and J.I. Mayordomo and R. Kumar and L.A. Kiemeney and M.L. Frigge and T. Jonsson and H. Saemundsson and R.B. Barkardottir and E. Jonsson and S. Jonsson and J.H. Olafsson and J.R. Gulcher and G. Masson and D.F. Gudbjartsson and A. Kong and U. Thorsteinsdottir and K. Stefansson",

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doi = "10.1038/ng.296",

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Rafnar, T, Sulem, P, Stacey, SN, Geller, F, Gudmundsson, J, Sigurdsson, A, Jakobsdottir, M, Helgadottir, H, Thorlacius, S, Aben, KK, Blondal, T, Thorgeirsson, TE, Thorleifsson, G, Kristjansson, K, Thorisdottir, K, Ragnarsson, R, Sigurgeirsson, B, Skuladottir, H, Gudbjartsson, T, Isaksson, HJ, Einarsson, GV, Benediktsdottir, KR, Agnarsson, BA, Olafsson, K, Salvarsdottir, A, Bjarnason, H, Asgeirsdottir, M, Kristinsson, KT, Matthiasdottir, S, Sveinsdottir, SG, Polidoro, S, Hoiom, V, Botella Estrada, R, Hemminki, K, Rudnai, P, Bishop, DT, Campagna, M, Kellen, E, Zeegers, MP, de Verdier, P, Ferrer, A, Isla, D, Vidal, MJ, Andres, R, Saez, B, Juberias, P, Banzo, J, Navarrete, S, Tres, A, Kan, D, Lindblom, A, Gurzau, E, Koppova, K, van de Vegt, F, Schalken, JA, van der Heijden, HF, Smit, HJ, Termeer, RA, Oosterwijk, E, van Hooij, O, Nagore, E, Porru, S, Steineck, G, Hansson, J, Buntinx, F, Catalona, WJ, Matullo, G, Vineis, P, Kiltie, AE, Mayordomo, JI, Kumar, R, Kiemeney, LA, Frigge, ML, Jonsson, T, Saemundsson, H, Barkardottir, RB, Jonsson, E, Jonsson, S, Olafsson, JH, Gulcher, JR, Masson, G, Gudbjartsson, DF, Kong, A, Thorsteinsdottir, U & Stefansson, K 2009, 'Sequence variants at the TERT-CLPTM1L locus associate with many cancer types', Nature Genetics, vol. 41, no. 2, pp. 221-7. https://doi.org/10.1038/ng.296

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. / Rafnar, T.; Sulem, P.; Stacey, S.N.; Geller, F.; Gudmundsson, J.; Sigurdsson, A.; Jakobsdottir, M.; Helgadottir, H.; Thorlacius, S.; Aben, K.K.; Blondal, T.; Thorgeirsson, T.E.; Thorleifsson, G.; Kristjansson, K.; Thorisdottir, K.; Ragnarsson, R.; Sigurgeirsson, B.; Skuladottir, H.; Gudbjartsson, T.; Isaksson, H.J.; Einarsson, G.V.; Benediktsdottir, K.R.; Agnarsson, B.A.; Olafsson, K.; Salvarsdottir, A.; Bjarnason, H.; Asgeirsdottir, M.; Kristinsson, K.T.; Matthiasdottir, S.; Sveinsdottir, S.G.; Polidoro, S.; Hoiom, V.; Botella Estrada, R.; Hemminki, K.; Rudnai, P.; Bishop, D.T.; Campagna, M.; Kellen, E.; Zeegers, M.P.; de Verdier, P.; Ferrer, A.; Isla, D.; Vidal, M.J.; Andres, R.; Saez, B.; Juberias, P.; Banzo, J.; Navarrete, S.; Tres, A.; Kan, D.; Lindblom, A.; Gurzau, E.; Koppova, K.; van de Vegt, F.; Schalken, J.A.; van der Heijden, H.F.; Smit, H.J.; Termeer, R.A.; Oosterwijk, E.; van Hooij, O.; Nagore, E.; Porru, S.; Steineck, G.; Hansson, J.; Buntinx, F.; Catalona, W.J.; Matullo, G.; Vineis, P.; Kiltie, A.E.; Mayordomo, J.I.; Kumar, R.; Kiemeney, L.A.; Frigge, M.L.; Jonsson, T.; Saemundsson, H.; Barkardottir, R.B.; Jonsson, E.; Jonsson, S.; Olafsson, J.H.; Gulcher, J.R.; Masson, G.; Gudbjartsson, D.F.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K.

In: Nature Genetics, Vol. 41, No. 2, 01.01.2009, p. 221-7.

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

TY - JOUR

T1 - Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

AU - Rafnar, T.

AU - Sulem, P.

AU - Stacey, S.N.

AU - Geller, F.

AU - Gudmundsson, J.

AU - Sigurdsson, A.

AU - Jakobsdottir, M.

AU - Helgadottir, H.

AU - Thorlacius, S.

AU - Aben, K.K.

AU - Blondal, T.

AU - Thorgeirsson, T.E.

AU - Thorleifsson, G.

AU - Kristjansson, K.

AU - Thorisdottir, K.

AU - Ragnarsson, R.

AU - Sigurgeirsson, B.

AU - Skuladottir, H.

AU - Gudbjartsson, T.

AU - Isaksson, H.J.

AU - Einarsson, G.V.

AU - Benediktsdottir, K.R.

AU - Agnarsson, B.A.

AU - Olafsson, K.

AU - Salvarsdottir, A.

AU - Bjarnason, H.

AU - Asgeirsdottir, M.

AU - Kristinsson, K.T.

AU - Matthiasdottir, S.

AU - Sveinsdottir, S.G.

AU - Polidoro, S.

AU - Hoiom, V.

AU - Botella Estrada, R.

AU - Hemminki, K.

AU - Rudnai, P.

AU - Bishop, D.T.

AU - Campagna, M.

AU - Kellen, E.

AU - Zeegers, M.P.

AU - de Verdier, P.

AU - Ferrer, A.

AU - Isla, D.

AU - Vidal, M.J.

AU - Andres, R.

AU - Saez, B.

AU - Juberias, P.

AU - Banzo, J.

AU - Navarrete, S.

AU - Tres, A.

AU - Kan, D.

AU - Lindblom, A.

AU - Gurzau, E.

AU - Koppova, K.

AU - van de Vegt, F.

AU - Schalken, J.A.

AU - van der Heijden, H.F.

AU - Smit, H.J.

AU - Termeer, R.A.

AU - Oosterwijk, E.

AU - van Hooij, O.

AU - Nagore, E.

AU - Porru, S.

AU - Steineck, G.

AU - Hansson, J.

AU - Buntinx, F.

AU - Catalona, W.J.

AU - Matullo, G.

AU - Vineis, P.

AU - Kiltie, A.E.

AU - Mayordomo, J.I.

AU - Kumar, R.

AU - Kiemeney, L.A.

AU - Frigge, M.L.

AU - Jonsson, T.

AU - Saemundsson, H.

AU - Barkardottir, R.B.

AU - Jonsson, E.

AU - Jonsson, S.

AU - Olafsson, J.H.

AU - Gulcher, J.R.

AU - Masson, G.

AU - Gudbjartsson, D.F.

AU - Kong, A.

AU - Thorsteinsdottir, U.

AU - Stefansson, K.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

AB - The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

U2 - 10.1038/ng.296

DO - 10.1038/ng.296

M3 - Article

C2 - 19151717

VL - 41

SP - 221

EP - 227

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -