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

• DOI: 10.1038/ng.161
• Publication Date: 2008-05-18T19:01:11Z
• Authors: Daniel F Gudbjart...; Patrick Sulem; Simon N Stacey; Alisa M Goldstein; Thorunn Rafnar; Bardur Sigurgeirsson; Kristrun R Benedi...; Kristin Thorisdottir; Rafn Ragnarsson; Steinunn G Sveins...; Veronica Magnusson; Annika Lindblom; Konstantinos Kost...; Rafael Botella-Es...; Virtudes Soriano; Pablo Juberías; Matilde Grasa; Berta Saez; Raquel Andres; Dominique Scherer; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Lambertus A Kiemeney; Margret Jakobsdottir; Stacy Steinberg; Agnar Helgason; Solveig Gretarsdo...; Margaret A Tucker; José I Mayordomo; Eduardo Nagore; Rajiv Kumar; Johan Hansson; Jon H Olafsson; Jeffrey Gulcher; Augustine Kong; Unnur Thorsteinsd...; Kari Stefansson
• Keywords: Adult; Adolescent; 03 medical and health sciences; 0302 clinical medicine; Gene Frequency; ONCOL 1: Hereditary cancer and cancer-related syndromes; Odds Ratio; Humans; Genetic Predisposition to Disease; Neoplasm Metastasis; Melanoma; Aged; Aged, 80 and over; Membrane Glycoproteins; Eye Color; Monophenol Monooxygenase; Pigmentation; Middle Aged; NCEBP 1: Molecular epidemiology; ONCOL 5: Aetiology, screening and detection; 3. Good health; Europe; ONCOL 3: Translational research; Carcinoma, Basal Cell; Case-Control Studies; Agouti Signaling Protein; UMCN 1.2: Molecular diagnosis, prognosis and monitoring; Oxidoreductases

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 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 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 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.