This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rudd, M. F. Search for Related Content PubMed PubMed Citation Articles by Rudd, M. F. Social Bookmarking                   What's this?

Letter

Variants in the GH-IGF axis confer susceptibilityto lung cancer

¹ Section of Cancer Genetics, ² Section of Paediatrics ³ Section of Medicine, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom

We conducted a large-scale genome-wide association study in UK Caucasians to identify susceptibility alleles for lung cancer, analyzing 1529 cases and 2707 controls. To increase the likelihood of identifying disease-causing alleles, we genotyped 1476 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 871 candidate cancer genes, biasing SNP selection toward those predicted to be deleterious. Statistically significant associations were identified for 64 nsSNPs, generating a genome-wide significance level of P = 0.002. Eleven of the 64 SNPs mapped to genes encoding pivotal components of the growth hormone/insulin-like growth factor (GH-IGF) pathway, including CAMKK1 E375G (OR = 1.37, P = 5.4 x 10^–5), AKAP9 M463I (OR = 1.32, P = 1.0 x 10^–4) and GHR P495T (OR = 12.98, P = 0.0019). Significant associations were also detected for SNPs within genes in the DNA damage-response pathway, including BRCA2 K3326X (OR = 1.72, P = 0.0075) and XRCC4 I137T (OR = 1.31, P = 0.0205). Our study provides evidence that inherited predisposition to lung cancer is in part mediated through low-penetrance alleles and specifically identifies variants in GH-IGF and DNA damage-response pathways with risk of lung cancer.

⁵ Corresponding author.

E-mail Richard.Houlston{at}icr.ac.uk; fax 4-20-8722-4359.

⁶ List of GELCAPS Consortium collaborators available on request.

[Supplemental material is available online at www.genome.org.]

Article is online at http://www.genome.org/cgi/doi/10.1101/gr.5120106

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Cao, H. Lu, J. Feng, J. Shu, D. Zheng, and Y. Hou Lung Cancer Risk Associated with Thr495Pro Polymorphism of GHR in Chinese Population Jpn. J. Clin. Oncol., April 1, 2008; 38(4): 308 - 316. [Abstract] [Full Text] [PDF]

				B. Frank, M. Wiestler, S. Kropp, K. Hemminki, A. B. Spurdle, C. Sutter, B. Wappenschmidt, X. Chen, J. Beesley, J. L. Hopper, et al. Association of a Common AKAP9 Variant With Breast Cancer Risk: A Collaborative Analysis J Natl Cancer Inst, March 19, 2008; 100(6): 437 - 442. [Abstract] [Full Text] [PDF]

				R. J. Hung, M. Baragatti, D. Thomas, J. McKay, N. Szeszenia-Dabrowska, D. Zaridze, J. Lissowska, P. Rudnai, E. Fabianova, D. Mates, et al. Inherited Predisposition of Lung Cancer: A Hierarchical Modeling Approach to DNA Repair and Cell Cycle Control Pathways Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2736 - 2744. [Abstract] [Full Text] [PDF]

				C. I. Amos Successful design and conduct of genome-wide association studies Hum. Mol. Genet., October 15, 2007; 16(R2): R220 - R225. [Abstract] [Full Text] [PDF]

				N. Johnson, O. Fletcher, C. Palles, M. Rudd, E. Webb, G. Sellick, I. dos Santos Silva, V. McCormack, L. Gibson, A. Fraser, et al. Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility Hum. Mol. Genet., May 1, 2007; 16(9): 1051 - 1057. [Abstract] [Full Text] [PDF]

				R. A. George, J. Y. Liu, L. L. Feng, R. J. Bryson-Richardson, D. Fatkin, and M. A. Wouters Analysis of protein sequence and interaction data for candidate disease gene prediction Nucleic Acids Res., November 14, 2006; 34(19): e130 - e130. [Abstract] [Full Text] [PDF]