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.
Stacey
Simon N
SN
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
Gudbjartsson
Daniel F
DF
Sulem
Patrick
P
Bergthorsson
Jon T
JT
Kumar
Rajiv
R
Thorleifsson
Gudmar
G
Sigurdsson
Asgeir
A
Jakobsdottir
Margret
M
Sigurgeirsson
Bardur
B
Benediktsdottir
Kristrun R
KR
Thorisdottir
Kristin
K
Ragnarsson
Rafn
R
Scherer
Dominique
D
Rudnai
Peter
P
Gurzau
Eugene
E
Koppova
Kvetoslava
K
Höiom
Veronica
V
Botella-Estrada
Rafael
R
Soriano
Virtudes
V
Juberías
Pablo
P
Grasa
Matilde
M
Carapeto
Francisco J
FJ
Tabuenca
Pilar
P
Gilaberte
Yolanda
Y
Gudmundsson
Julius
J
Thorlacius
Steinunn
S
Helgason
Agnar
A
Thorlacius
Theodora
T
Jonasdottir
Aslaug
A
Blondal
Thorarinn
T
Gudjonsson
Sigurjon A
SA
Jonsson
Gudbjörn F
GF
Saemundsdottir
Jona
J
Kristjansson
Kristleifur
K
Bjornsdottir
Gyda
G
Sveinsdottir
Steinunn G
SG
Mouy
Magali
M
Geller
Frank
F
Nagore
Eduardo
E
Mayordomo
José I
JI
Hansson
Johan
J
Rafnar
Thorunn
T
Kong
Augustine
A
Olafsson
Jon H
JH
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
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