Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits.
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
Simon N
SN
Stacey
Daniel F
DF
Gudbjartsson
Patrick
P
Sulem
Jon T
JT
Bergthorsson
Rajiv
R
Kumar
Gudmar
G
Thorleifsson
Asgeir
A
Sigurdsson
Margret
M
Jakobsdottir
Bardur
B
Sigurgeirsson
Kristrun R
KR
Benediktsdottir
Kristin
K
Thorisdottir
Rafn
R
Ragnarsson
Dominique
D
Scherer
Peter
P
Rudnai
Eugene
E
Gurzau
Kvetoslava
K
Koppova
Veronica
V
Höiom
Rafael
R
Botella-Estrada
Virtudes
V
Soriano
Pablo
P
Juberías
Matilde
M
Grasa
Francisco J
FJ
Carapeto
Pilar
P
Tabuenca
Yolanda
Y
Gilaberte
Julius
J
Gudmundsson
Steinunn
S
Thorlacius
Agnar
A
Helgason
Theodora
T
Thorlacius
Aslaug
A
Jonasdottir
Thorarinn
T
Blondal
Sigurjon A
SA
Gudjonsson
Gudbjörn F
GF
Jonsson
Jona
J
Saemundsdottir
Kristleifur
K
Kristjansson
Gyda
G
Bjornsdottir
Steinunn G
SG
Sveinsdottir
Magali
M
Mouy
Frank
F
Geller
Eduardo
E
Nagore
José I
JI
Mayordomo
Johan
J
Hansson
Thorunn
T
Rafnar
Augustine
A
Kong
Jon H
JH
Olafsson
Unnur
U
Thorsteinsdottir
Kari
K
Stefansson
D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000483:Alleles; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D010858:Pigmentation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012313:RNA / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D020662:Guanine Nucleotide Exchange Factors; C477650:RCC2 protein, human; D012313:RNA