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

Thorunn Rafnar*, Patrick Sulem, Simon N. Stacey, Frank Geller, Julius Gudmundsson, Asgeir Sigurdsson, Margret Jakobsdottir, Hafdis Helgadottir, Steinunn Thorlacius, Katja K.H. Aben, Thorarinn Blöndal, Thorgeir E. Thorgeirsson, Gudmar Thorleifsson, Kristleifur Kristjansson, Kristin Thorisdottir, Rafn Ragnarsson, Bardur Sigurgeirsson, Halla Skuladottir, Tomas Gudbjartsson, Helgi J. IsakssonGudmundur V. Einarsson, Kristrun R. Benediktsdottir, Bjarni A. Agnarsson, Karl Olafsson, Anna Salvarsdottir, Hjordis Bjarnason, Margret Asgeirsdottir, Kari T. Kristinsson, Sigurborg Matthiasdottir, Steinunn G. Sveinsdottir, Silvia Polidoro, Veronica Höiom, Rafael Botella-Estrada, Kari Hemminki, Peter Rudnai, D. Timothy Bishop, Marcello Campagna, Eliane Kellen, Maurice P. Zeegers, Petra De Verdier, Ana Ferrer, Dolores Isla, Maria Jesus Vidal, Raquel Andres, Berta Saez, Pablo Juberias, Javier Banzo, Sebastian Navarrete, Alejandro Tres, Donghui Kan, Annika Lindblom, Eugene Gurzau, Kvetoslava Koppova, Femmie De Vegt, Jack A. Schalken, Henricus F.M. Van Der Heijden, Hans J. Smit, René A. Termeer, Egbert Oosterwijk, Onno Van Hooij, Eduardo Nagore, Stefano Porru, Gunnar Steineck, Johan Hansson, Frank Buntinx, William J. Catalona, Giuseppe Matullo, Paolo Vineis, Anne E. Kiltie, José I. Mayordomo, Rajiv Kumar, Lambertus A. Kiemeney, Michael L. Frigge, Thorvaldur Jonsson, Hafsteinn Saemundsson, Rosa B. Barkardottir, Eirikur Jonsson, Steinn Jonsson, Jon H. Olafsson, Jeffrey R. Gulcher, Gisli Masson, Daniel F. Gudbjartsson, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

474 Citations (Scopus)

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 × 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 × 10-8) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 × 10-4). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 × 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.

Original languageEnglish
Pages (from-to)221-227
Number of pages7
JournalNature Genetics
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 2009

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