title: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.
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 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.
authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. daniel.gudbjartsson@decode.is
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Bardur
authors.initials: B
authors.lastname: Sigurgeirsson
authors.forename: Kristrun R
authors.initials: KR
authors.lastname: Benediktsdottir
authors.forename: Kristin
authors.initials: K
authors.lastname: Thorisdottir
authors.forename: Rafn
authors.initials: R
authors.lastname: Ragnarsson
authors.forename: Steinunn G
authors.initials: SG
authors.lastname: Sveinsdottir
authors.forename: Veronica
authors.initials: V
authors.lastname: Magnusson
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostulas
authors.forename: Rafael
authors.initials: R
authors.lastname: Botella-Estrada
authors.forename: Virtudes
authors.initials: V
authors.lastname: Soriano
authors.forename: Pablo
authors.initials: P
authors.lastname: Juberías
authors.forename: Matilde
authors.initials: M
authors.lastname: Grasa
authors.forename: Berta
authors.initials: B
authors.lastname: Saez
authors.forename: Raquel
authors.initials: R
authors.lastname: Andres
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Eugene
authors.initials: E
authors.lastname: Gurzau
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Koppova
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Margret
authors.initials: M
authors.lastname: Jakobsdottir
authors.forename: Stacy
authors.initials: S
authors.lastname: Steinberg
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: José I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nagore
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Jon H
authors.initials: JH
authors.lastname: Olafsson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054366:Agouti Signaling Protein / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005060:Europe; D005127:Eye Color / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D010088:Oxidoreductases / Q000235:genetics; D010858:Pigmentation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012042:Registries; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C515182:ASIP protein, human; D054366:Agouti Signaling Protein; D008562:Membrane Glycoproteins; D044102:Receptor, Melanocortin, Type 1; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase