ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.
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.
Gudbjartsson
Daniel F
DF
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. daniel.gudbjartsson@decode.is
Sulem
Patrick
P
Stacey
Simon N
SN
Goldstein
Alisa M
AM
Rafnar
Thorunn
T
Sigurgeirsson
Bardur
B
Benediktsdottir
Kristrun R
KR
Thorisdottir
Kristin
K
Ragnarsson
Rafn
R
Sveinsdottir
Steinunn G
SG
Magnusson
Veronica
V
Lindblom
Annika
A
Kostulas
Konstantinos
K
Botella-Estrada
Rafael
R
Soriano
Virtudes
V
Juberías
Pablo
P
Grasa
Matilde
M
Saez
Berta
B
Andres
Raquel
R
Scherer
Dominique
D
Rudnai
Peter
P
Gurzau
Eugene
E
Koppova
Kvetoslava
K
Kiemeney
Lambertus A
LA
Jakobsdottir
Margret
M
Steinberg
Stacy
S
Helgason
Agnar
A
Gretarsdottir
Solveig
S
Tucker
Margaret A
MA
Mayordomo
José I
JI
Nagore
Eduardo
E
Kumar
Rajiv
R
Hansson
Johan
J
Olafsson
Jon H
JH
Gulcher
Jeffrey
J
Kong
Augustine
A
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
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
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