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

2.50
Hdl Handle:
http://hdl.handle.net/10146/82638
Title:
Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.
Authors:
Rafnar, Thorunn; Sulem, Patrick; Stacey, Simon N.; Geller, Frank; Gudmundsson, Julius; Sigurdsson, Asgeir; Jakobsdottir, Margret; Helgadottir, Hafdis; Thorlacius, Steinunn; Aben, Katja K.H.; Blondal, 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; Hoiom, 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, Rene 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
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.
Affiliation:
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. thorunn.rafnar@decode.is
Citation:
Nat. Genet. 2009, 41 (2):221-227
Journal:
Nature genetics
Issue Date:
Feb-2009
URI:
http://hdl.handle.net/10146/82638
DOI:
10.1038/ng.296
PubMed ID:
19151717
Additional Links:
http://www.nature.com/ng/journal/v41/n2/abs/ng.296.html
Type:
Article
Language:
en
ISSN:
1546-1718
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorRafnar, Thorunnen
dc.contributor.authorSulem, Patricken
dc.contributor.authorStacey, Simon N.en
dc.contributor.authorGeller, Franken
dc.contributor.authorGudmundsson, Juliusen
dc.contributor.authorSigurdsson, Asgeiren
dc.contributor.authorJakobsdottir, Margreten
dc.contributor.authorHelgadottir, Hafdisen
dc.contributor.authorThorlacius, Steinunnen
dc.contributor.authorAben, Katja K.H.en
dc.contributor.authorBlondal, Thorarinnen
dc.contributor.authorThorgeirsson, Thorgeir E.en
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorKristjansson, Kristleifuren
dc.contributor.authorThorisdottir, Kristinen
dc.contributor.authorRagnarsson, Rafnen
dc.contributor.authorSigurgeirsson, Barduren
dc.contributor.authorSkuladottir, Hallaen
dc.contributor.authorGudbjartsson, Tomasen
dc.contributor.authorIsaksson, Helgi J.en
dc.contributor.authorEinarsson, Gudmundur V.en
dc.contributor.authorBenediktsdottir, Kristrun R.en
dc.contributor.authorAgnarsson, Bjarni A.en
dc.contributor.authorOlafsson, Karlen
dc.contributor.authorSalvarsdottir, Annaen
dc.contributor.authorBjarnason, Hjordisen
dc.contributor.authorAsgeirsdottir, Margreten
dc.contributor.authorKristinsson, Kari T.en
dc.contributor.authorMatthiasdottir, Sigurborgen
dc.contributor.authorSveinsdottir, Steinunn G.en
dc.contributor.authorPolidoro, Silviaen
dc.contributor.authorHoiom, Veronicaen
dc.contributor.authorBotella-Estrada, Rafaelen
dc.contributor.authorHemminki, Karien
dc.contributor.authorRudnai, Peteren
dc.contributor.authorBishop, D. Timothyen
dc.contributor.authorCampagna, Marcelloen
dc.contributor.authorKellen, Elianeen
dc.contributor.authorZeegers, Maurice P.en
dc.contributor.authorde Verdier, Petraen
dc.contributor.authorFerrer, Anaen
dc.contributor.authorIsla, Doloresen
dc.contributor.authorVidal, Maria Jesusen
dc.contributor.authorAndres, Raquelen
dc.contributor.authorSaez, Bertaen
dc.contributor.authorJuberias, Pabloen
dc.contributor.authorBanzo, Javieren
dc.contributor.authorNavarrete, Sebastianen
dc.contributor.authorTres, Alejandroen
dc.contributor.authorKan, Donghuien
dc.contributor.authorLindblom, Annikaen
dc.contributor.authorGurzau, Eugeneen
dc.contributor.authorKoppova, Kvetoslavaen
dc.contributor.authorde Vegt, Femmieen
dc.contributor.authorSchalken, Jack A.en
dc.contributor.authorvan der Heijden, Henricus F.M.en
dc.contributor.authorSmit, Hans J.en
dc.contributor.authorTermeer, Rene A.en
dc.contributor.authorOosterwijk, Egberten
dc.contributor.authorvan Hooij, Onnoen
dc.contributor.authorNagore, Eduardoen
dc.contributor.authorPorru, Stefanoen
dc.contributor.authorSteineck, Gunnaren
dc.contributor.authorHansson, Johanen
dc.contributor.authorBuntinx, Franken
dc.contributor.authorCatalona, William J.en
dc.contributor.authorMatullo, Giuseppeen
dc.contributor.authorVineis, Paoloen
dc.contributor.authorKiltie, Anne E.en
dc.contributor.authorMayordomo, José I.en
dc.contributor.authorKumar, Rajiven
dc.contributor.authorKiemeney, Lambertus A.en
dc.contributor.authorFrigge, Michael L.en
dc.contributor.authorJonsson, Thorvalduren
dc.contributor.authorSaemundsson, Hafsteinnen
dc.contributor.authorBarkardottir, Rosa B.en
dc.contributor.authorJonsson, Eirikuren
dc.contributor.authorJonsson, Steinnen
dc.contributor.authorOlafsson, Jon H.en
dc.contributor.authorGulcher, Jeffrey R.en
dc.contributor.authorMasson, Gislien
dc.contributor.authorGudbjartsson, Daniel F.en
dc.contributor.authorKong, Augustineen
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorStefansson, Karien
dc.date.accessioned2009-09-25T08:26:15Z-
dc.date.available2009-09-25T08:26:15Z-
dc.date.issued2009-02-
dc.identifier.citationNat. Genet. 2009, 41 (2):221-227en
dc.identifier.issn1546-1718-
dc.identifier.pmid19151717-
dc.identifier.doi10.1038/ng.296-
dc.identifier.urihttp://hdl.handle.net/10146/82638-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.relation.urlhttp://www.nature.com/ng/journal/v41/n2/abs/ng.296.htmlen
dc.subjectCarcinomaen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectLinkage Disequilibriumen
dc.subjectNeoplasm Proteinsen
dc.subjectNeoplasmsen
dc.subjectQuantitative Trait Locien
dc.subjectSkin Neoplasmsen
dc.subjectTelomeraseen
dc.subject.meshAged-
dc.subject.meshCarcinoma, Basal Cell-
dc.subject.meshCase-Control Studies-
dc.subject.meshFemale-
dc.subject.meshGene Frequency-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshMale-
dc.subject.meshMembrane Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshNeoplasms-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshQuantitative Trait Loci-
dc.subject.meshSkin Neoplasms-
dc.subject.meshTelomerase-
dc.titleSequence variants at the TERT-CLPTM1L locus associate with many cancer types.en
dc.typeArticleen
dc.contributor.departmentdeCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. thorunn.rafnar@decode.isen
dc.identifier.journalNature geneticsen

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