Variants in the GH-IGF axis confer susceptibility to lung cancer.


Rudd, MF; Webb, EL; Matakidou, A; Sellick, GS; Williams, RD; Bridle, H; Eisen, T; Houlston, RS; GELCAPS Consortium, ; (2006) Variants in the GH-IGF axis confer susceptibility to lung cancer. Genome research, 16 (6). pp. 693-701. ISSN 1088-9051 DOI: https://doi.org/10.1101/gr.5120106

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Abstract

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=5.4x10(-5)), AKAP9 M463I (OR=1.32, P=1.0x10(-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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 16741161
Web of Science ID: 237973200001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2425

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