Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice
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.
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.
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.
KeywordsHereditary colorectal cancer Polyposis Cancer risk assessment Genetic counseling Cancer genetic testing Next-generation sequencing panel
The primary author acknowledges Heather Stern for her editorial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal rights and informed consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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