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

521 Citations (Scopus)


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
Issue number2
Publication statusPublished - Feb 2009

Bibliographical note

Funding Information:
We thank the individuals that participated in the study and whose contribution made this work possible. We also thank the nurses at deCODE’s participant recruitment center and the personnel at deCODE’s core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic subjects with cancer. The project was funded in part by the European Commission (POLYGENE: LSHC-CT-2005-018827 and GENADDICT: LSHM-CT-2004-005166), the National Institutes of Health (R01-DA017932) and a research investment grant of the Radboud University Nijmegen Medical Centre. The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (Contract No 513943); and by a grant of the compagnia di San Paolo, the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata. J.H. is supported by the Swedish Cancer Society, The Radiumhemmet Research Funds, The Swedish Research Council and the Karolinska Institutet Research Funds.


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