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Hereditary colorectal cancer syndromes

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Abstract

The purpose of this article is to review the genetic colorectal cancer syndromes including Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Family Polyposis (FAP) and the hamartomatous polyposis syndromes. HNPCC is the most common of the hereditary colorectal cancer syndromes, and is the result of defects in the mismatch repair genes. Individuals with HNPCC have an 80 lifetime risk of colorectal cancer, and in females a 30–50% risk of endometrial cancer, as well as predisposition for a number of other malignancies. Early screening and interval surveillance for colorectal and endometrial cancer are recommended. In FAP, mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene give rise to hundreds to thousands of colorectal polyps, some of which will inevitably progress to cancer. Early diagnosis and timely prophylactic colectomy prevent this outcome. Chemoprevention with nonsteroidal anti-inflammatory drugs can reduce adenoma number and size in FAP, but the effect is incomplete. In addtion, surveillance for upper gastrointestinal tract malignancies is necessary. Attenuated forms of FAP may be the result of mutations in the APC gene, or in the recently described MYH gene. Mutations in the MYH gene should be considered in individuals with multiple adenomas whose family history does not reflect an autosomal dominant pattern of inheritance. The hamartomatous polyposis syndromes are uncommon but distinctive disorders in which multiple hamartomatous polyps develop at a young age. Our understanding of the genetic basis of these disorders is improving, and a predisposition for gastrointestinal and other malignancies has recently been recognized. This article summarizes the genetics, clinical manifestations and clinical management of each of these syndromes with an emphasis on genetic testing and prevention.

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Authors and Affiliations

  1. Division of Population Sciences, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA

    Lisa L. Strate & Sapna Syngal

  2. Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, USA

    Lisa L. Strate & Sapna Syngal

  3. Harvard Medical School, Boston, MA, USA

    Lisa L. Strate & Sapna Syngal

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  1. Lisa L. Strate
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Strate, L.L., Syngal, S. Hereditary colorectal cancer syndromes. Cancer Causes Control 16, 201–213 (2005). https://doi.org/10.1007/s10552-004-3488-4

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