New common variants affecting susceptibility to basal cell carcinoma

Simon N. Stacey; Patrick Sulem; Gisli Masson; Sigurjon A. Gudjonsson; Gudmar Thorleifsson; Margret Jakobsdottir; Asgeir Sigurdsson; Daniel F. Gudbjartsson; Bardur Sigurgeirsson; Kristrun R. Benediktsdottir; Kristin Thorisdottir; Rafn Ragnarsson; Dominique Scherer; Kari Hemminki; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Rafael Botella-Estrada; Virtudes Soriano; Pablo Juberias; Berta Saez; Yolanda Gilaberte; Victoria Fuentelsaz; Cristina Corredera; Matilde Grasa; Veronica Höiom; Annika Lindblom; Johannes J. Bonenkamp; Michelle M. Van Rossum; Katja K H Aben; Esther De Vries; Mario Santinami; Maria G. Di Mauro; Andrea Maurichi; Judith Wendt; Pia Hochleitner; Hubert Pehamberger; Julius Gudmundsson; Droplaug N. Magnusdottir; Solveig Gretarsdottir; Hilma Holm; Valgerdur Steinthorsdottir; Michael L. Frigge; Thorarinn Blondal; Jona Saemundsdottir; Hjördis Bjarnason; Kristleifur Kristjansson; Gyda Bjornsdottir; Ichiro Okamoto; Licia Rivoltini; Monica Rodolfo; Lambertus A. Kiemeney; Johan Hansson; Eduardo Nagore; José I. Mayordomo; Rajiv Kumar; Margaret R. Karagas; Heather H. Nelson; Jeffrey R. Gulcher; Thorunn Rafnar; Unnur Thorsteinsdottir; Jon H. Olafsson; Augustine Kong; Kari Stefansson

doi:10.1038/ng.412

New common variants affecting susceptibility to basal cell carcinoma

Simon N. Stacey, Patrick Sulem, Gisli Masson, Sigurjon A. Gudjonsson, Gudmar Thorleifsson, Margret Jakobsdottir, Asgeir Sigurdsson, Daniel F. Gudbjartsson, Bardur Sigurgeirsson, Kristrun R. Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Dominique Scherer, Kari Hemminki, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Rafael Botella-Estrada, Virtudes Soriano, Pablo JuberiasBerta Saez, Yolanda Gilaberte, Victoria Fuentelsaz, Cristina Corredera, Matilde Grasa, Veronica Höiom, Annika Lindblom, Johannes J. Bonenkamp, Michelle M. Van Rossum, Katja K H Aben, Esther De Vries, Mario Santinami, Maria G. Di Mauro, Andrea Maurichi, Judith Wendt, Pia Hochleitner, Hubert Pehamberger, Julius Gudmundsson, Droplaug N. Magnusdottir, Solveig Gretarsdottir, Hilma Holm, Valgerdur Steinthorsdottir, Michael L. Frigge, Thorarinn Blondal, Jona Saemundsdottir, Hjördis Bjarnason, Kristleifur Kristjansson, Gyda Bjornsdottir, Ichiro Okamoto, Licia Rivoltini, Monica Rodolfo, Lambertus A. Kiemeney, Johan Hansson, Eduardo Nagore, José I. Mayordomo, Rajiv Kumar, Margaret R. Karagas, Heather H. Nelson, Jeffrey R. Gulcher, Thorunn Rafnar, Unnur Thorsteinsdottir, Jon H. Olafsson, Augustine Kong, Kari Stefansson

Epidemiology & Community Health

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

279 Scopus citations

Abstract

In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10 ^-9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10 ^-9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10 ^-10). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.

Original language	English (US)
Pages (from-to)	909-914
Number of pages	6
Journal	Nature Genetics
Volume	41
Issue number	8
DOIs	https://doi.org/10.1038/ng.412
State	Published - Aug 2009

Bibliographical note

Funding Information:
We thank G.H. Olafsdottir and L. Tryggvadottir of the Icelandic Cancer Registry for assistance with the ascertainment of affected individuals, S. Sveinsdottir for assistance with subject recruitment, and H. Sigurdsson for assistance with the figures. We are grateful to I. Saaf for permission to reproduce a section of the Human Intermediate Filament Database in Supplementary Figure 1. This study was supported in part by the Jubilaumsfonds of the Austrian National Bank (project numbers 11946 and 12161), the Swedish Cancer Society, the Radiumhemmet Research Funds and the Swedish Research Council, the US National Institute of Environmental Health Sciences (T32E007155), the US National Institutes of Health (R01CA082354 and R01CA57494), and a Research Investment Grant of the Radboud University Nijmegen Medical Centre.

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Stacey, S. N., Sulem, P., Masson, G., Gudjonsson, S. A., Thorleifsson, G., Jakobsdottir, M., Sigurdsson, A., Gudbjartsson, D. F., Sigurgeirsson, B., Benediktsdottir, K. R., Thorisdottir, K., Ragnarsson, R., Scherer, D., Hemminki, K., Rudnai, P., Gurzau, E., Koppova, K., Botella-Estrada, R., Soriano, V., ... Stefansson, K. (2009). New common variants affecting susceptibility to basal cell carcinoma. Nature Genetics, 41(8), 909-914. https://doi.org/10.1038/ng.412

Stacey, SN, Sulem, P, Masson, G, Gudjonsson, SA, Thorleifsson, G, Jakobsdottir, M, Sigurdsson, A, Gudbjartsson, DF, Sigurgeirsson, B, Benediktsdottir, KR, Thorisdottir, K, Ragnarsson, R, Scherer, D, Hemminki, K, Rudnai, P, Gurzau, E, Koppova, K, Botella-Estrada, R, Soriano, V, Juberias, P, Saez, B, Gilaberte, Y, Fuentelsaz, V, Corredera, C, Grasa, M, Höiom, V, Lindblom, A, Bonenkamp, JJ, Van Rossum, MM, Aben, KKH, De Vries, E, Santinami, M, Di Mauro, MG, Maurichi, A, Wendt, J, Hochleitner, P, Pehamberger, H, Gudmundsson, J, Magnusdottir, DN, Gretarsdottir, S, Holm, H, Steinthorsdottir, V, Frigge, ML, Blondal, T, Saemundsdottir, J, Bjarnason, H, Kristjansson, K, Bjornsdottir, G, Okamoto, I, Rivoltini, L, Rodolfo, M, Kiemeney, LA, Hansson, J, Nagore, E, Mayordomo, JI, Kumar, R, Karagas, MR, Nelson, HH, Gulcher, JR, Rafnar, T, Thorsteinsdottir, U, Olafsson, JH, Kong, A & Stefansson, K 2009, 'New common variants affecting susceptibility to basal cell carcinoma', Nature Genetics, vol. 41, no. 8, pp. 909-914. https://doi.org/10.1038/ng.412

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title = "New common variants affecting susceptibility to basal cell carcinoma",

abstract = "In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10 -9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10 -9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10 -10). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.",

author = "Stacey, {Simon N.} and Patrick Sulem and Gisli Masson and Gudjonsson, {Sigurjon A.} and Gudmar Thorleifsson and Margret Jakobsdottir and Asgeir Sigurdsson and Gudbjartsson, {Daniel F.} and Bardur Sigurgeirsson and Benediktsdottir, {Kristrun R.} and Kristin Thorisdottir and Rafn Ragnarsson and Dominique Scherer and Kari Hemminki and Peter Rudnai and Eugene Gurzau and Kvetoslava Koppova and Rafael Botella-Estrada and Virtudes Soriano and Pablo Juberias and Berta Saez and Yolanda Gilaberte and Victoria Fuentelsaz and Cristina Corredera and Matilde Grasa and Veronica H{\"o}iom and Annika Lindblom and Bonenkamp, {Johannes J.} and {Van Rossum}, {Michelle M.} and Aben, {Katja K H} and {De Vries}, Esther and Mario Santinami and {Di Mauro}, {Maria G.} and Andrea Maurichi and Judith Wendt and Pia Hochleitner and Hubert Pehamberger and Julius Gudmundsson and Magnusdottir, {Droplaug N.} and Solveig Gretarsdottir and Hilma Holm and Valgerdur Steinthorsdottir and Frigge, {Michael L.} and Thorarinn Blondal and Jona Saemundsdottir and Hj{\"o}rdis Bjarnason and Kristleifur Kristjansson and Gyda Bjornsdottir and Ichiro Okamoto and Licia Rivoltini and Monica Rodolfo and Kiemeney, {Lambertus A.} and Johan Hansson and Eduardo Nagore and Mayordomo, {Jos{\'e} I.} and Rajiv Kumar and Karagas, {Margaret R.} and Nelson, {Heather H.} and Gulcher, {Jeffrey R.} and Thorunn Rafnar and Unnur Thorsteinsdottir and Olafsson, {Jon H.} and Augustine Kong and Kari Stefansson",

note = "Funding Information: We thank G.H. Olafsdottir and L. Tryggvadottir of the Icelandic Cancer Registry for assistance with the ascertainment of affected individuals, S. Sveinsdottir for assistance with subject recruitment, and H. Sigurdsson for assistance with the figures. We are grateful to I. Saaf for permission to reproduce a section of the Human Intermediate Filament Database in Supplementary Figure 1. This study was supported in part by the Jubilaumsfonds of the Austrian National Bank (project numbers 11946 and 12161), the Swedish Cancer Society, the Radiumhemmet Research Funds and the Swedish Research Council, the US National Institute of Environmental Health Sciences (T32E007155), the US National Institutes of Health (R01CA082354 and R01CA57494), and a Research Investment Grant of the Radboud University Nijmegen Medical Centre.",

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month = aug,

doi = "10.1038/ng.412",

language = "English (US)",

volume = "41",

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issn = "1061-4036",

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T1 - New common variants affecting susceptibility to basal cell carcinoma

AU - Stacey, Simon N.

AU - Sulem, Patrick

AU - Masson, Gisli

AU - Gudjonsson, Sigurjon A.

AU - Thorleifsson, Gudmar

AU - Jakobsdottir, Margret

AU - Sigurdsson, Asgeir

AU - Gudbjartsson, Daniel F.

AU - Sigurgeirsson, Bardur

AU - Benediktsdottir, Kristrun R.

AU - Thorisdottir, Kristin

AU - Ragnarsson, Rafn

AU - Scherer, Dominique

AU - Hemminki, Kari

AU - Rudnai, Peter

AU - Gurzau, Eugene

AU - Koppova, Kvetoslava

AU - Botella-Estrada, Rafael

AU - Soriano, Virtudes

AU - Juberias, Pablo

AU - Saez, Berta

AU - Gilaberte, Yolanda

AU - Fuentelsaz, Victoria

AU - Corredera, Cristina

AU - Grasa, Matilde

AU - Höiom, Veronica

AU - Lindblom, Annika

AU - Bonenkamp, Johannes J.

AU - Van Rossum, Michelle M.

AU - Aben, Katja K H

AU - De Vries, Esther

AU - Santinami, Mario

AU - Di Mauro, Maria G.

AU - Maurichi, Andrea

AU - Wendt, Judith

AU - Hochleitner, Pia

AU - Pehamberger, Hubert

AU - Gudmundsson, Julius

AU - Magnusdottir, Droplaug N.

AU - Gretarsdottir, Solveig

AU - Holm, Hilma

AU - Steinthorsdottir, Valgerdur

AU - Frigge, Michael L.

AU - Blondal, Thorarinn

AU - Saemundsdottir, Jona

AU - Bjarnason, Hjördis

AU - Kristjansson, Kristleifur

AU - Bjornsdottir, Gyda

AU - Okamoto, Ichiro

AU - Rivoltini, Licia

AU - Rodolfo, Monica

AU - Kiemeney, Lambertus A.

AU - Hansson, Johan

AU - Nagore, Eduardo

AU - Mayordomo, José I.

AU - Kumar, Rajiv

AU - Karagas, Margaret R.

AU - Nelson, Heather H.

AU - Gulcher, Jeffrey R.

AU - Rafnar, Thorunn

AU - Thorsteinsdottir, Unnur

AU - Olafsson, Jon H.

AU - Kong, Augustine

AU - Stefansson, Kari

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PY - 2009/8

Y1 - 2009/8

N2 - In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10 -9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10 -9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10 -10). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.

AB - In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10 -9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10 -9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10 -10). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.

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New common variants affecting susceptibility to basal cell carcinoma

Abstract

Bibliographical note

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