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

作者：Gudbjartsson Daniel F^*; Sulem Patrick; Stacey Simon N; Goldstein Alisa M; Rafnar Thorunn; Sigurgeirsson Bardur; Benediktsdottir Kristrun R; Thorisdottir Kristin; Ragnarsson Rafn; Sveinsdottir Steinunn G; Magnusson Veronica; Lindblom Annika; Kostulas Konstantinos; Botella Estrada Rafael; Soriano Virtudes; Juberias Pablo; Grasa Matilde; Saez Berta; Andres Raquel; Scherer Dominique; Rudnai Peter; Gurzau Eugene; Koppova Kvetoslava; Kiemeney Lambertus A

来源：Nature Genetics, 2008, 40(7): 886-891.

DOI：10.1038/ng.161

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.

• 出版日期2008-7