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PMID: 19151717 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

Nature genetics ·Vol. 41 ·No. 2 ·2009-02-00 ·Pages 221-7

Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blöndal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, Polidoro S, Höiom V, Botella-Estrada R, Hemminki K, Rudnai P, Bishop DT, Campagna M, Kellen E, Zeegers MP, de Verdier P, Ferrer A, Isla D, Vidal MJ, Andres R, Saez B, Juberias P, Banzo J, Navarrete S, Tres A, Kan D, Lindblom A, Gurzau E, Koppova K, de Vegt F, Schalken JA, van der Heijden HF, Smit HJ, Termeer RA, Oosterwijk E, van Hooij O, Nagore E, Porru S, Steineck G, Hansson J, Buntinx F, Catalona WJ, Matullo G, Vineis P, Kiltie AE, Mayordomo JI, Kumar R, Kiemeney LA, Frigge ML, Jonsson T, Saemundsson H, Barkardottir RB, Jonsson E, Jonsson S, Olafsson JH, Gulcher JR, Masson G, Gudbjartsson DF, Kong A, Thorsteinsdottir U, Stefansson K

Abstract

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.

MeSH Terms
Aged Carcinoma, Basal Cell/genetics Case-Control Studies Female Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Male Membrane Proteins/genetics Middle Aged Neoplasm Proteins/genetics Neoplasms/genetics Polymorphism, Single Nucleotide/physiology Quantitative Trait Loci Skin Neoplasms/genetics Telomerase/genetics
Chemicals
CLPTM1L protein, human Membrane Proteins Neoplasm Proteins TERT protein, human Telomerase
Authors & Affiliations
85 authors, click to expand affiliations / ORCID
Rafnar Thorunn
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. [email protected]
Sulem Patrick
Stacey Simon N
Geller Frank
Gudmundsson Julius
Sigurdsson Asgeir
Jakobsdottir Margret
Helgadottir Hafdis
Thorlacius Steinunn
Aben Katja K H
Blöndal Thorarinn
Thorgeirsson Thorgeir E
Thorleifsson Gudmar
Kristjansson Kristleifur
Thorisdottir Kristin
Ragnarsson Rafn
Sigurgeirsson Bardur
Skuladottir Halla
Gudbjartsson Tomas
Isaksson Helgi J
Einarsson Gudmundur V
Benediktsdottir Kristrun R
Agnarsson Bjarni A
Olafsson Karl
Salvarsdottir Anna
Bjarnason Hjordis
Asgeirsdottir Margret
Kristinsson Kari T
Matthiasdottir Sigurborg
Sveinsdottir Steinunn G
Polidoro Silvia
Höiom Veronica
Botella-Estrada Rafael
Hemminki Kari
Rudnai Peter
Bishop D Timothy
Campagna Marcello
Kellen Eliane
Zeegers Maurice P
de Verdier Petra
Ferrer Ana
Isla Dolores
Vidal Maria Jesus
Andres Raquel
Saez Berta
Juberias Pablo
Banzo Javier
Navarrete Sebastian
Tres Alejandro
Kan Donghui
Lindblom Annika
Gurzau Eugene
Koppova Kvetoslava
de Vegt Femmie
Schalken Jack A
van der Heijden Henricus F M
Smit Hans J
Termeer René A
Oosterwijk Egbert
van Hooij Onno
Nagore Eduardo
Porru Stefano
Steineck Gunnar
Hansson Johan
Buntinx Frank
Catalona William J
Matullo Giuseppe
Vineis Paolo
Kiltie Anne E
Mayordomo José I
Kumar Rajiv
Kiemeney Lambertus A
Frigge Michael L
Jonsson Thorvaldur
Saemundsson Hafsteinn
Barkardottir Rosa B
Jonsson Eirikur
Jonsson Steinn
Olafsson Jon H
Gulcher Jeffrey R
Masson Gisli
Gudbjartsson Daniel F
Kong Augustine
Thorsteinsdottir Unnur
Stefansson Kari
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.296
Email
[email protected]
Published
2009-02-00
Epub
2009-00-18
Pages
221-7
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4525478
Subset
IM
Grants
Cancer Research UK · 10589 · United Kingdom
Cancer Research UK · A4994 · United Kingdom
NIDA NIH HHS · R01 DA017932 · United States
NIDA NIH HHS · R01-DA017932 · United States
External Links
PubMed source DOI: 10.1038/ng.296 PMC Full Text View journal details
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