Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: Refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genes

LG Carvajal-Carmona; JB Cazier; AM Jones; K Howarth; P Broderick; A Pittman; S Dobbins; A Tenesa; S Farrington; J Prendergast; E Theodoratou; R Barnetson; D Conti; P Newcomb; JL Hopper; MA Jenkins; S Gallinger; DJ Duggan; H Campbell; D Kerr; G Casey; R Houlston; M Dunlop; I Tomlinson

Journal article

Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: Refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genes

LG Carvajal-Carmona, JB Cazier, AM Jones, K Howarth, P Broderick, A Pittman, S Dobbins, A Tenesa, S Farrington, J Prendergast, E Theodoratou, R Barnetson, D Conti, P Newcomb, JL Hopper, MA Jenkins, S Gallinger, DJ Duggan, H Campbell, D Kerr Show all

Human Molecular Genetics | Published : 2011

DOI: 10.1093/hmg/ddr190

Abstract

We have previously identified several colorectal cancer (CRC)-associated polymorphisms using genome-wide association (GWA) analysis. We sought to fine-map the location of the functional variants for three of these regions at 8q23.3 (EIF3H), 16q22.1 (CDH1/CDH3) and 19q13.11 (RHPN2). We genotyped two case-control sets at high density in the selected regions and used existing data from four other case-control sets, compris- ing a total of 9328 CRC cases and 10 480 controls. To improve marker density, we imputed genotypes from the 1000 Genomes Project and Hapmap3 data sets. All three regions contained smaller areas in which a cluster of single nucleotide polymorphisms (SNPs) showed clearly stron..

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University of Melbourne Researchers

Mark Jenkins Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

Cancer Research UK provided principal funding for this study. The Oxford Comprehensive Biomedical Research Centre (I.T.) and the EU FP7 CHIBCHA grant (to L.G.C.-C. and I.T.) also provided funding. Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford, was provided by grant 075491/Z/04. The Medical Research Council (G0000657-53203), CORE and Scottish Executive Chief Scientist's Office (K/OPR/2/2/D333, CZB/4/449) provided additional funding (to M.D.). The Colon Cancer Family Registry was supported by the National Cancer Institute and National Institutes of Health under Request for Application #CA-95-011, and through cooperative agreements with the Australian Colorectal Cancer Family Registry (UO1 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (UO1 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (UO1 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (UO1 CA074783), Seattle Colorectal Cancer Family Registry (UO1 CA074794) and The University of Hawaii Colorectal Cancer Family Registry (UO1 CA074806).