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Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice

  • Genetics in Gastroenterology Practice (B Katona, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

A Correction to this article was published on 23 December 2019

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Abstract

Purpose of review

Decades have passed since the underlying molecular etiologies of the most common hereditary forms of colorectal cancer (CRC), Lynch syndrome, and familial adenomatous polyposis (FAP) were first described. With the advent of next-generation sequencing (NGS) panels, the landscape of hereditary CRC testing has changed dramatically. We review available screening strategies, novel CRC predisposition genes, and challenges and opportunities in this field.

Recent findings

Improved sensitivity and availability of NGS panel testing have greatly expanded our understanding regarding the number of CRC syndromes and their phenotypic expression. A variety of screening strategies are available to identify heritable CRC syndromes, potentially decreasing morbidity and mortality in this population. However, these screening strategies remain imperfect and present challenges regarding their implementation in clinical practice. Screening strategies include universal screening of CRC tumors for Lynch syndrome, clinical prediction algorithms, and risk assessment questionnaires. Additionally, there remains a gap in our understanding of the clinical implications of novel gene mutations of variable penetrance and unexpected NGS panel test results. Incorporation of single nucleotide polymorphisms (SNPs) may help to further refine cancer risk assessment, and the clinical introduction of RNA analysis may allow us to clarify variants of unknown significance (VUSs) and identify deep intronic mutations that would otherwise be missed.

Summary

Recognition of genetic predisposition to CRC is critical for the practicing gastroenterologist. The evolving field of cancer genetics offers great challenges and opportunities for improved CRC management.

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Change history

  • 23 December 2019

    The original article unfortunately contained a mistake. On page 8, Table 2, the row with “POLE POLD1” has been shifted right so all the columns are not correct.

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Acknowledgements

The primary author acknowledges Heather Stern for her editorial support.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, 200 Campus Dr, Suite 2400|Entrance 4, Hershey, PA, 17033, USA

    Benjamin Stern DO & Thomas McGarrity MD

  2. Division of Hematology Oncology, Penn State Health Milton S. Hershey Medical Center, Penn State Cancer Institute, 400 University Dr, Hershey, PA, 17033, USA

    Maria Baker PhD, MS

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  1. Benjamin Stern DO
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Correspondence to Benjamin Stern DO.

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References for readers

PREMM5 model = https://premm.dfci.harvard.edu/

GeneReviews® = https://www.ncbi.nlm.nih.gov/books/NBK1116/

2019 NCCN guidelines = https://www.nccn.org

National Society of Genetics Counselors = www.nsgc.org

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Stern, B., McGarrity, T. & Baker, M. Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice. Curr Treat Options Gastro 17, 702–715 (2019). https://doi.org/10.1007/s11938-019-00267-w

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