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TGF-β Signaling Alterations and Colon Cancer

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Cancer Genetics

Part of the book series: Cancer Treatment and Research ((CTAR,volume 155))

Abstract

Colorectal cancer is the second most common cause of cancer-related death in the United States. Twin studies suggest that 35% of all colorectal cancer cases are inherited. High-penetrance tumor susceptibility genes account for at most 3–6% of all colorectal cancer cases and the remainder of the unexplained risk is likely due to a combination of low to moderate penetrance genes. Recent genome-wide association studies have identified several SNPs near genes belonging to the transforming growth factor beta (TGF-β) superfamily such as GREM1 and SMAD7. Together with the recent discovery that constitutively decreased TGFBR1 expression is a potent modifier of colorectal cancer risk, these findings strongly suggest that germline variants of the TGF-β superfamily may account for a sizeable proportion of colorectal cancer cases. The TGF-β superfamily signaling pathways mediate many different biological processes during embryonic development, and in adult organisms they play a role in tissue homeostasis. TGF-β has a central role in inhibiting cell proliferation and also modulates processes such as cell invasion, immune regulation, and microenvironment modification. Mutations in the TGF-β type II receptor (TGFBR2) are estimated to occur in approximately 30% of colorectal carcinomas. Mutations in SMAD4 and BMPR1A are found in patients with familial juvenile polyposis, an autosomal dominant condition associated with an increased risk of colorectal cancer. This chapter provides an overview of the genetic basis of colorectal cancer and discusses recent discoveries related to alterations in the TGF-β pathways and their role in the development of colorectal cancer.

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Acknowledgments

This work is supported by grants R01 CA108741, R01 CA112520, R01 137000, and P60 AR048098 from NIH.

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  1. Division of Hematology/Oncology, Department of Medicine UAB Comprehensive Cancer Center, The University of Alabama, 35294-3300, Birmingham, AL, USA

    Naresh Bellam & Boris Pasche

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  1. Naresh Bellam
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  2. Boris Pasche
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  1. The UAB Comprehensive Cancer Center, Division of Hematology/Oncology, The University of Alabama at Birmingham, Birmingham, 35294-3300, Alabama, USA

    Boris Pasche

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Bellam, N., Pasche, B. (2010). TGF-β Signaling Alterations and Colon Cancer. In: Pasche, B. (eds) Cancer Genetics. Cancer Treatment and Research, vol 155. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-6033-7_5

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