Abstract
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 × 10−9) and BCC (OR = 1.35, P = 1.2 × 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 × 10−7) and BCC (OR = 1.14, P = 6.1 × 10−4). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.3 × 10−4). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.
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Change history
29 July 2008
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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Acknowledgements
The Swedish part of the study received financial support from the Swedish Cancer Society, the Radiumhemmet Research Funds and the Swedish Research Council. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, by a subcontract agreement to deCODE Genetics under Westat contract N02-CP-91026 to the National Cancer Institute.
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D.F.G., P.S., S.N.S. and K.S. wrote the first draft of the paper. S.N.S., B. Sigurgeirsson, K.R.B., K.T., R.R., S.G.S. and J.H.O. collected the Icelandic samples and phenotypes. V.M., A.L., K. Kostulas, S.G. and J.H. collected the Swedish samples and phenotypes. R.B.-E., V.S., P.J., M.G., B. Saez, R.A., J.I.M. and E.N. collected the Spanish samples and phenotypes. D.S., P.R., E.G., K.Koppova and R.K. collected the Eastern European samples and phenotypes. S.N.S., M.J. and U.T. performed the genotyping. D.F.G., P.S., S.S. and A.H. analyzed the data. D.F.G., P.S., S.N.S., A.M.G., T.R., L.A.K., M.A.T., J.I.M., E.N., R.K., J.H., J.H.O., J.G., A.K., U.T. and K.S. planned, coordinated and supervised the work. All authors contributed to the final version of the paper.
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Gudbjartsson, D., Sulem, P., Stacey, S. et al. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet 40, 886–891 (2008). https://doi.org/10.1038/ng.161
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DOI: https://doi.org/10.1038/ng.161
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