Letter abstract

Nature Genetics 40, 886 - 891 (2008)
Published online: 18 May 2008 | Corrected online: 29 July 2008 | doi:10.1038/ng.161

There is a Corrigendum (August 2008) associated with this Letter.

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Daniel F Gudbjartsson1,22, Patrick Sulem1,22, Simon N Stacey1,22, Alisa M Goldstein2, Thorunn Rafnar1, Bardur Sigurgeirsson3,4, Kristrun R Benediktsdottir3,4, Kristin Thorisdottir3,4,5, Rafn Ragnarsson5, Steinunn G Sveinsdottir6, Veronica Magnusson7, Annika Lindblom8, Konstantinos Kostulas9, Rafael Botella-Estrada10, Virtudes Soriano11, Pablo Juberías12, Matilde Grasa12, Berta Saez13, Raquel Andres14, Dominique Scherer15, Peter Rudnai16, Eugene Gurzau17, Kvetoslava Koppova18, Lambertus A Kiemeney19,20,21, Margret Jakobsdottir1, Stacy Steinberg1, Agnar Helgason1, Solveig Gretarsdottir1, Margaret A Tucker2, José I Mayordomo14, Eduardo Nagore11, Rajiv Kumar15, Johan Hansson7, Jon H Olafsson3,4, Jeffrey Gulcher1, Augustine Kong1, Unnur Thorsteinsdottir1 & Kari Stefansson1


Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 times 10-9) and BCC (OR = 1.35, P = 1.2 times 10-6). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 times 10-7) and BCC (OR = 1.14, P = 6.1 times 10-4). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.3 times 10-4). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.

  1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
  2. Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
  3. Department of Dermatology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
  4. Department of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
  5. Department of Plastic Surgery, Landspitali-University Hospital, 101 Reykjavik, Iceland.
  6. Clinical Research Center, 110 Reykjavik, Iceland.
  7. Department of Oncology Pathology, Cancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm S171 76, Sweden.
  8. Department of Molecular Medicine, Karolinska Institute, S171 76 Stockholm, Sweden.
  9. Department of Neurology, Karolinska Institutet at Karolinska University Hospital, Huddinge S141 86, Sweden.
  10. Department of Dermatology, Instituto Valenciano de Oncologia, Valencia 46009, Spain.
  11. Department of Oncology, Instituto Valenciano de Oncologia, Valencia 46009, Spain.
  12. Division of Dermatology, University Hospital, Zaragoza 50009, Spain.
  13. Health Science Institute, Zaragoza 50009, Spain.
  14. Division of Medical Oncology, University Hospital, Zaragoza 50009, Spain.
  15. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg D-69120, Germany.
  16. National Institute of Environmental Health, Budapest H-1450, Hungary.
  17. Environmental Health Center, Cluj, RO-Cluj-Napoca, Romania.
  18. State Health Institute, Banska Bystrica, SK-975 56, Slovakia.
  19. Comprehensive Cancer Center, Nijmegen 6501BG, The Netherlands.
  20. Department of Epidemiology and Biostatistics, Radboud University, Nijmegen Medical Center, Nijmegen 6500HB, The Netherlands.
  21. Department of Urology, Radboud University, Nijmegen Medical Center, Nijmegen 6500HB, The Netherlands.
  22. These authors contributed equally to the paper.

Correspondence to: Daniel F Gudbjartsson1,22 e-mail: daniel.gudbjartsson@decode.is

Correspondence to: Kari Stefansson1 e-mail: kstefans@decode.is

* In the version of this article initially published, there were two errors in the numbers reported in the abstract. The correct odds ratio for the association of the ASIP haplotype with risk of basal cell carcinoma is 1.35, and the correct P value for the association of the TYRP1 variant with risk of cutaneous melanoma is 4.3 x 10-4. These errors have been corrected in the HTML and PDF versions of the article.


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