Use of Family History and Genetic Testing to Determine Risk of Colorectal Cancer

Gastroenterology. 2020 Jan;158(2):389-403. doi: 10.1053/j.gastro.2019.11.029. Epub 2019 Nov 21.


Approximately 35% of patients with colorectal cancer (CRC) have a family history of the disease attributed to genetic factors, common exposures, or both. Some families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5% to 10% of CRC cases. Most families with a history of CRC and/or adenomas do not carry genetic variants associated with cancer syndromes; this is called common familial CRC. Our understanding of familial predisposition to CRC and cancer syndromes has increased rapidly due to advances in next-generation sequencing technologies. As a result, there has been a shift from genetic testing for specific inherited cancer syndromes based on clinical criteria alone, to simultaneous testing of multiple genes for cancer-associated variants. We summarize current knowledge of common familial CRC, provide an update on syndromes associated with CRC (including the nonpolyposis and polyposis types), and review current recommendations for CRC screening and surveillance. We also provide an approach to genetic evaluation and testing in clinical practice. Determination of CRC risk based on family cancer history and results of genetic testing can provide a personalized approach to cancer screening and prevention, with optimal use of colonoscopy to effectively decrease CRC incidence and mortality.

Keywords: Colorectal Cancer Genetic Risk Assessment; Familial Colorectal Cancer; Inherited Colorectal Cancer Syndromes.

Publication types

  • Review

MeSH terms

  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / prevention & control
  • Early Detection of Cancer / methods
  • Early Detection of Cancer / standards*
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Medical History Taking / standards*
  • Practice Guidelines as Topic
  • Precision Medicine / methods
  • Precision Medicine / standards
  • Risk Assessment / methods
  • Risk Assessment / standards
  • Risk Factors