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Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk

Abstract

We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 × 10−14).

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Figure 1: P values throughout the region of study.

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Acknowledgements

We are very grateful to all individuals in the study; colleagues at Clinical Genetics Centres and the National Cancer Research Network, S. Whitelaw and staff colleagues at St. Mark's Hospital for work on HMPS, the Genome Centre at the Institute of Cancer, Bart's and the London Medical School, and the Equipment Park, London Research Institute, Cancer Research UK. Cancer Research UK provided principal funding for this study. Additional funding was provided by CORE, the European Union (CPRB LSHC-CT-2004-503465) and the Bobby Moore Fund.

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Authors and Affiliations

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Contributions

E.J. undertook the bulk of the laboratory work on HMPS, with assistance from K.H. and A.R. Laboratory work on the common variants was undertaken by E.J., K.H., L.C.C., A.R., P.B., S.S., A.P., A.W., Z.K., K.S., S.L., E.D., I.C. and E.P. E.W., S.S. and J.B.C. undertook data analysis. E.B., L.M., M.G., J.V., W.W., S.P. and M.Q. recruited subjects. The CORGI Consortium, D.K., R.G. and J.P. planned and supervised recruitment of subjects. H.T. co-planned the work on HMPS and was part of the CORGI Consortium. S.F., A.T., M.D. and H.C. were involved in study planning. R.H. and I.T. planned and supervised the study, obtained grant funding and co-wrote the manuscript.

Corresponding authors

Correspondence to Richard Houlston or Ian Tomlinson.

Additional information

A full list of consortium members is provided in Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1–3, Supplementary Figures 1 and 2, Supplementary Note (PDF 227 kb)

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Jaeger, E., Webb, E., Howarth, K. et al. Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat Genet 40, 26–28 (2008). https://doi.org/10.1038/ng.2007.41

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  • DOI: https://doi.org/10.1038/ng.2007.41

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