Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

Simon N. Stacey, Daniel F. Gudbjartsson, Patrick Sulem, Jon T. Bergthorsson, Rajiv Kumar, Gudmar Thorleifsson, Asgeir Sigurdsson, Margret Jakobsdottir, Bardur Sigurgeirsson, Kristrun R. Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Dominique Scherer, P. Rudnai, Eugene Gurzau, Kvetoslava Koppova, Veronica Höiom, Rafael Botella-Estrada, Virtudes Soriano, Pablo Juberías & 26 others Matilde Grasa, Francisco J. Carapeto, Pilar Tabuenca, Yolanda Gilaberte, Julius Gudmundsson, Steinunn Thorlacius, Agnar Helgason, Theodora Thorlacius, Aslaug Jonasdottir, Thorarinn Blondal, Sigurjon A. Gudjonsson, Gudbjörn F. Jonsson, Jona Saemundsdottir, Kristleifur Kristjansson, Gyda Bjornsdottir, Steinunn G. Sveinsdottir, Magali Mouy, Frank Geller, Eduardo Nagore, José I. Mayordomo, Johan Hansson, Thorunn Rafnar, Augustine Kong, Jon H. Olafsson, Unnur Thorsteinsdottir, Kari Stefansson

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Abstract

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 × 10-12) and rs801114 on 1q42 (OR = 1.28, P = 5.9 × 10 -12). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

Original languageEnglish
Pages (from-to)1313-1318
Number of pages6
JournalNature Genetics
Volume40
Issue number11
DOIs
Publication statusPublished - Nov 2008

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Basal Cell Carcinoma
Pigmentation
Melanoma
Skin
Single Nucleotide Polymorphism
Iceland
Eastern Europe
Genome-Wide Association Study
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Stacey, S. N., Gudbjartsson, D. F., Sulem, P., Bergthorsson, J. T., Kumar, R., Thorleifsson, G., ... Stefansson, K. (2008). Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nature Genetics, 40(11), 1313-1318. https://doi.org/10.1038/ng.234

Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. / Stacey, Simon N.; Gudbjartsson, Daniel F.; Sulem, Patrick; Bergthorsson, Jon T.; Kumar, Rajiv; Thorleifsson, Gudmar; Sigurdsson, Asgeir; Jakobsdottir, Margret; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Scherer, Dominique; Rudnai, P.; Gurzau, Eugene; Koppova, Kvetoslava; Höiom, Veronica; Botella-Estrada, Rafael; Soriano, Virtudes; Juberías, Pablo; Grasa, Matilde; Carapeto, Francisco J.; Tabuenca, Pilar; Gilaberte, Yolanda; Gudmundsson, Julius; Thorlacius, Steinunn; Helgason, Agnar; Thorlacius, Theodora; Jonasdottir, Aslaug; Blondal, Thorarinn; Gudjonsson, Sigurjon A.; Jonsson, Gudbjörn F.; Saemundsdottir, Jona; Kristjansson, Kristleifur; Bjornsdottir, Gyda; Sveinsdottir, Steinunn G.; Mouy, Magali; Geller, Frank; Nagore, Eduardo; Mayordomo, José I.; Hansson, Johan; Rafnar, Thorunn; Kong, Augustine; Olafsson, Jon H.; Thorsteinsdottir, Unnur; Stefansson, Kari.

In: Nature Genetics, Vol. 40, No. 11, 11.2008, p. 1313-1318.

Research output: Contribution to journalArticle

Stacey, SN, Gudbjartsson, DF, Sulem, P, Bergthorsson, JT, Kumar, R, Thorleifsson, G, Sigurdsson, A, Jakobsdottir, M, Sigurgeirsson, B, Benediktsdottir, KR, Thorisdottir, K, Ragnarsson, R, Scherer, D, Rudnai, P, Gurzau, E, Koppova, K, Höiom, V, Botella-Estrada, R, Soriano, V, Juberías, P, Grasa, M, Carapeto, FJ, Tabuenca, P, Gilaberte, Y, Gudmundsson, J, Thorlacius, S, Helgason, A, Thorlacius, T, Jonasdottir, A, Blondal, T, Gudjonsson, SA, Jonsson, GF, Saemundsdottir, J, Kristjansson, K, Bjornsdottir, G, Sveinsdottir, SG, Mouy, M, Geller, F, Nagore, E, Mayordomo, JI, Hansson, J, Rafnar, T, Kong, A, Olafsson, JH, Thorsteinsdottir, U & Stefansson, K 2008, 'Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits', Nature Genetics, vol. 40, no. 11, pp. 1313-1318. https://doi.org/10.1038/ng.234
Stacey SN, Gudbjartsson DF, Sulem P, Bergthorsson JT, Kumar R, Thorleifsson G et al. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nature Genetics. 2008 Nov;40(11):1313-1318. https://doi.org/10.1038/ng.234
Stacey, Simon N. ; Gudbjartsson, Daniel F. ; Sulem, Patrick ; Bergthorsson, Jon T. ; Kumar, Rajiv ; Thorleifsson, Gudmar ; Sigurdsson, Asgeir ; Jakobsdottir, Margret ; Sigurgeirsson, Bardur ; Benediktsdottir, Kristrun R. ; Thorisdottir, Kristin ; Ragnarsson, Rafn ; Scherer, Dominique ; Rudnai, P. ; Gurzau, Eugene ; Koppova, Kvetoslava ; Höiom, Veronica ; Botella-Estrada, Rafael ; Soriano, Virtudes ; Juberías, Pablo ; Grasa, Matilde ; Carapeto, Francisco J. ; Tabuenca, Pilar ; Gilaberte, Yolanda ; Gudmundsson, Julius ; Thorlacius, Steinunn ; Helgason, Agnar ; Thorlacius, Theodora ; Jonasdottir, Aslaug ; Blondal, Thorarinn ; Gudjonsson, Sigurjon A. ; Jonsson, Gudbjörn F. ; Saemundsdottir, Jona ; Kristjansson, Kristleifur ; Bjornsdottir, Gyda ; Sveinsdottir, Steinunn G. ; Mouy, Magali ; Geller, Frank ; Nagore, Eduardo ; Mayordomo, José I. ; Hansson, Johan ; Rafnar, Thorunn ; Kong, Augustine ; Olafsson, Jon H. ; Thorsteinsdottir, Unnur ; Stefansson, Kari. / Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. In: Nature Genetics. 2008 ; Vol. 40, No. 11. pp. 1313-1318.
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abstract = "To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 × 10-12) and rs801114 on 1q42 (OR = 1.28, P = 5.9 × 10 -12). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6{\%} of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.",
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T1 - Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

AU - Stacey, Simon N.

AU - Gudbjartsson, Daniel F.

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AU - Bergthorsson, Jon T.

AU - Kumar, Rajiv

AU - Thorleifsson, Gudmar

AU - Sigurdsson, Asgeir

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AU - Sigurgeirsson, Bardur

AU - Benediktsdottir, Kristrun R.

AU - Thorisdottir, Kristin

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AU - Höiom, Veronica

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AU - Grasa, Matilde

AU - Carapeto, Francisco J.

AU - Tabuenca, Pilar

AU - Gilaberte, Yolanda

AU - Gudmundsson, Julius

AU - Thorlacius, Steinunn

AU - Helgason, Agnar

AU - Thorlacius, Theodora

AU - Jonasdottir, Aslaug

AU - Blondal, Thorarinn

AU - Gudjonsson, Sigurjon A.

AU - Jonsson, Gudbjörn F.

AU - Saemundsdottir, Jona

AU - Kristjansson, Kristleifur

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AU - Sveinsdottir, Steinunn G.

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AU - Nagore, Eduardo

AU - Mayordomo, José I.

AU - Hansson, Johan

AU - Rafnar, Thorunn

AU - Kong, Augustine

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AU - Thorsteinsdottir, Unnur

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N2 - To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 × 10-12) and rs801114 on 1q42 (OR = 1.28, P = 5.9 × 10 -12). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

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