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Energy Balance and Gastrointestinal Cancer pp 23–45Cite as

Genetics of Colon Cancer Susceptibility

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Part of the book series: Energy Balance and Cancer ((EBAC,volume 4))

Abstract

Colorectal cancer (CRC) exhibits a strong familial risk with first-degree relatives of cases having a two to three times greater risk of developing CRC than the general population. An estimated 35% of CRC cases are due to genetic factors. Highly penetrant predisposing genes have been identified for several inherited CRC syndromes (e.g., FAP, Lynch syndrome, and juvenile polyposis) through genetic linkage studies. However, despite these considerable successes, mutations in these rare syndromes explain less than 6% of CRCs and only a small fraction of familial risk. While two recently described syndromes, MUTYH-associated polyposis, with its pattern of recessive inheritance, and familial CRC type X, account for additional genetic burden, they still account for only a small fraction of CRC risk. In the last few years, considerable effort has been directed toward the identification of common, low-penetrance mutations through the promising approach of genome-wide association studies (GWAS). With respect to CRC, 15 novel disease loci have been identified through GWAS including several genes involved in the TGFβ signaling pathway. The familial and population risks explained by these loci remain small, but it is expected that additional novel susceptibility markers will be identified as larger ongoing and pooled GWAS are completed. While the role of the majority of susceptibility genes identified through linkage studies and GWAS in energy balance remains unclear, a pattern is emerging of a possible link given that several TGFβ-related genes have been implicated in energy balance including susceptibility genes identified through linkage analyses or GWAS.

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  1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Graham Casey Ph.D.

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    Sanford D. Markowitz

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    Nathan A. Berger

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Casey, G. (2012). Genetics of Colon Cancer Susceptibility. In: Markowitz, S., Berger, N. (eds) Energy Balance and Gastrointestinal Cancer. Energy Balance and Cancer, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2367-6_2

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