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Review

COGENT (COlorectal cancer GENeTics) revisited

Richard S Houlston et al. Mutagenesis. 2012 Mar.

Abstract

Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT.

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Figures

Fig. 1
Fig. 1
Cumulative impact of the 14 variants on CRC risk. Distribution of risk alleles in controls (grey bars) and CRC cases (black bars) for the 14 loci (14).
Fig. 2
Fig. 2
Power to identify risk loci for CRC over a range of minor allele frequencies and relative risks. Illustrative study based on two-stage design—3000 cases and 3000 controls typed for 500 000 tagging SNPs in Stage 1 and 7000 cases and 7000 controls typed for 50 000 ‘top’ ranking SNPs in Stage 2. P-value in combined analysis thresholded at 10−5.
See this image and copyright information in PMC

References

    1. Aaltonen L, Johns L, Jarvinen H, Mecklin JP, Houlston R. Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin. Cancer Res. 2007;13:356–361. - PubMed
    1. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 2000;343:78–85. - PubMed
    1. Lubbe SJ, Webb EL, Chandler IP, Houlston RS. Implications of familial colorectal cancer risk profiles and microsatellite instability status. J. Clin. Oncol. 2009;27:2238–2244. - PubMed
    1. Houlston RS, Cheadle J, Dobbins SE, et al. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat. Genet. 2010;42:973–977. - PMC - PubMed
    1. Tomlinson I, Webb E, Carvajal-Carmona L, et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 2007;39:984–988. - PubMed

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