Lung cancer susceptibility locus at 5p15.33

Abstract

We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10−7 and P = 4 × 10−6) and replicated by the independent study series (P = 7 × 10−5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.

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Figure 1: Forest plot representing lung cancer risk and the two variants in the 5p region (rs402710 and rs2736100).

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Acknowledgements

The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. Support for the central Europe, HUNT2/Tromsø and CARET genome-wide studies and follow-up genotyping was provided by Institut National du Cancer, France. Support for the HUNT2/Tromsø genome-wide study was also provided by the European Community (Integrated Project DNA repair, grant no. LSHG-CT-2005-512113), the Norwegian Cancer Association and the Functional Genomics Programme of Research Council of Norway. Funding for the Toronto genome-wide study was provided by the Ontario Institute of Cancer Research. Funding for the Szczecin/Poland replication study was provided by European Community program “Marie-Curie Host Fellowships for the Transfer of Knowledge,” grant no. MTKD-CT-2004-510114. Additional funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Cancer Institute (R01 CA092039).

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P. Brennan and M. Lathrop designed the study. J.D.M., R.J.H., V.G., M.B.E., A.B. and H. Blanche coordinated the preparation and inclusion of all biological samples. J.D.M., S.H. and V.G. undertook the statistical analysis. Bioinformatics analysis was undertaken by F.M., M.F. and S.H. D.Z., D.L. and I.G. coordinated the genotyping of the central Europe samples. A.M. and R.J.H. coordinated the genotyping of the Toronto samples. J.D.M., D.Z., M.D., A.C., T.A. and H.E.K. coordinated the genotyping of the other studies. All other coauthors coordinated the initial recruitment and management of the studies. M. Lathrop obtained financial support for genotyping of the central Europe study; P. Brennan, R.J.H. and H.E.K. obtained financial support for genotyping of the other studies. P. Brennan and J.D.M. drafted the manuscript with substantial contributions from R.J.H. and M. Lathrop. All authors contributed to the final paper.

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Correspondence to Paul Brennan.

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A full list of authors appears at the end of this paper.

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Supplementary Figures 1–3, Supplementary Tables 1–4 and Supplementary Methods (PDF 1068 kb)

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McKay, J., Hung, R., Gaborieau, V. et al. Lung cancer susceptibility locus at 5p15.33. Nat Genet 40, 1404–1406 (2008). https://doi.org/10.1038/ng.254

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