New common variants affecting susceptibility to basal cell carcinoma.
In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.
Stacey
Simon N
SN
deCODE genetics, Reykjavik, Iceland. simon.stacey@decode.is
Sulem
Patrick
P
Masson
Gisli
G
Gudjonsson
Sigurjon A
SA
Thorleifsson
Gudmar
G
Jakobsdottir
Margret
M
Sigurdsson
Asgeir
A
Gudbjartsson
Daniel F
DF
Sigurgeirsson
Bardur
B
Benediktsdottir
Kristrun R
KR
Thorisdottir
Kristin
K
Ragnarsson
Rafn
R
Scherer
Dominique
D
Hemminki
Kari
K
Rudnai
Peter
P
Gurzau
Eugene
E
Koppova
Kvetoslava
K
Botella-Estrada
Rafael
R
Soriano
Virtudes
V
Juberias
Pablo
P
Saez
Berta
B
Gilaberte
Yolanda
Y
Fuentelsaz
Victoria
V
Corredera
Cristina
C
Grasa
Matilde
M
Höiom
Veronica
V
Lindblom
Annika
A
Bonenkamp
Johannes J
JJ
van Rossum
Michelle M
MM
Aben
Katja K H
KK
de Vries
Esther
E
Santinami
Mario
M
Di Mauro
Maria G
MG
Maurichi
Andrea
A
Wendt
Judith
J
Hochleitner
Pia
P
Pehamberger
Hubert
H
Gudmundsson
Julius
J
Magnusdottir
Droplaug N
DN
Gretarsdottir
Solveig
S
Holm
Hilma
H
Steinthorsdottir
Valgerdur
V
Frigge
Michael L
ML
Blondal
Thorarinn
T
Saemundsdottir
Jona
J
Bjarnason
Hjördis
H
Kristjansson
Kristleifur
K
Bjornsdottir
Gyda
G
Okamoto
Ichiro
I
Rivoltini
Licia
L
Rodolfo
Monica
M
Kiemeney
Lambertus A
LA
Hansson
Johan
J
Nagore
Eduardo
E
Mayordomo
José I
JI
Kumar
Rajiv
R
Karagas
Margaret R
MR
Nelson
Heather H
HH
Gulcher
Jeffrey R
JR
Rafnar
Thorunn
T
Thorsteinsdottir
Unnur
U
Olafsson
Jon H
JH
Kong
Augustine
A
Stefansson
Kari
K
D002280:Basal Cell Carcinoma / Q000150:complications / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D053555:Keratin-5 / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008545:Melanoma / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics*
C422445:CLPTM1L protein, human; D053555:Keratin-5; D008565:Membrane Proteins; D009363:Neoplasm Proteins