Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.
The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
Rafnar
Thorunn
T
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. thorunn.rafnar@decode.is
Sulem
Patrick
P
Stacey
Simon N
SN
Geller
Frank
F
Gudmundsson
Julius
J
Sigurdsson
Asgeir
A
Jakobsdottir
Margret
M
Helgadottir
Hafdis
H
Thorlacius
Steinunn
S
Aben
Katja K H
KK
Blöndal
Thorarinn
T
Thorgeirsson
Thorgeir E
TE
Thorleifsson
Gudmar
G
Kristjansson
Kristleifur
K
Thorisdottir
Kristin
K
Ragnarsson
Rafn
R
Sigurgeirsson
Bardur
B
Skuladottir
Halla
H
Gudbjartsson
Tomas
T
Isaksson
Helgi J
HJ
Einarsson
Gudmundur V
GV
Benediktsdottir
Kristrun R
KR
Agnarsson
Bjarni A
BA
Olafsson
Karl
K
Salvarsdottir
Anna
A
Bjarnason
Hjordis
H
Asgeirsdottir
Margret
M
Kristinsson
Kari T
KT
Matthiasdottir
Sigurborg
S
Sveinsdottir
Steinunn G
SG
Polidoro
Silvia
S
Höiom
Veronica
V
Botella-Estrada
Rafael
R
Hemminki
Kari
K
Rudnai
Peter
P
Bishop
D Timothy
DT
Campagna
Marcello
M
Kellen
Eliane
E
Zeegers
Maurice P
MP
de Verdier
Petra
P
Ferrer
Ana
A
Isla
Dolores
D
Vidal
Maria Jesus
MJ
Andres
Raquel
R
Saez
Berta
B
Juberias
Pablo
P
Banzo
Javier
J
Navarrete
Sebastian
S
Tres
Alejandro
A
Kan
Donghui
D
Lindblom
Annika
A
Gurzau
Eugene
E
Koppova
Kvetoslava
K
de Vegt
Femmie
F
Schalken
Jack A
JA
van der Heijden
Henricus F M
HF
Smit
Hans J
HJ
Termeer
René A
RA
Oosterwijk
Egbert
E
van Hooij
Onno
O
Nagore
Eduardo
E
Porru
Stefano
S
Steineck
Gunnar
G
Hansson
Johan
J
Buntinx
Frank
F
Catalona
William J
WJ
Matullo
Giuseppe
G
Vineis
Paolo
P
Kiltie
Anne E
AE
Mayordomo
José I
JI
Kumar
Rajiv
R
Kiemeney
Lambertus A
LA
Frigge
Michael L
ML
Jonsson
Thorvaldur
T
Saemundsson
Hafsteinn
H
Barkardottir
Rosa B
RB
Jonsson
Eirikur
E
Jonsson
Steinn
S
Olafsson
Jon H
JH
Gulcher
Jeffrey R
JR
Masson
Gisli
G
Gudbjartsson
Daniel F
DF
Kong
Augustine
A
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D040641:Quantitative Trait Loci; D012878:Skin Neoplasms / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase