Introduction: risk and screening based on family history of colorectal cancer

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Clinical practice guidelines for the prevention, early detection and management of colorectal cancer > Introduction: risk and screening based on family history of colorectal cancer

Evidence shows that family history of colorectal cancer is an important risk factor for developing the disease. Genes have been identified which, when inherited in a mutated form, substantially increase a person’s risk of colorectal cancer. The best studied of these genes include:

  • the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, mutations of which cause the hereditary cancer predisposition of Lynch syndrome (previously known as hereditary non-polyposis colorectal cancer)
  • the APC gene, mutation of which causes familial adenomatous polyposis (FAP)
  • the DNA base excision repair gene MUTYH, biallelic mutation of which causes MUTYH-associated polyposis.

These genetic disorders have an autosomal-dominant mode of transmission (mismatch repair genes and APC) or autosomal-recessive mode of transmission (MUTYH) within families, and cause a very high risk for cancer (see High-risk familial syndromes).

However, mutations in these genes cause fewer than 5% of all colorectal cancer cases and at most, only explain half of the reasons why family history is a risk factor for colorectal cancer.[1] The remainder of the observed increases in familial risk could be due in part to mutations in yet-to-be-discovered colorectal cancer susceptibility genes[2], polygenic factors such as single-nucleotide polymorphisms (SNPs)[3][4] or dietary and other lifestyle factors shared by family members. Many statistical models have been developed for colorectal cancer risk that include family history as well as other risk factors.[5] Due to limited resources, only family history is considered in this chapter.

Assessment of family history of colorectal cancer has two roles in cancer prevention and early detection:

  • to prioritise who should be tested for mutations in these genes
  • to inform decisions about the optimal timing, frequency and modality of screening.

This chapter provides estimates of risk of colorectal cancer and screening recommendations for people who have a family history of colorectal cancer, who are not known or suspected to have a genetic syndrome.

For information on screening strategies for specific high-risk familial syndromes, see:


  1. Aaltonen L, Johns L, Järvinen H, Mecklin JP, Houlston R. Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res 2007 Jan 1;13(1):356-61 Abstract available at
  2. Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, et al. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 2016 Oct 31 Abstract available at
  3. Hsu L, Jeon J, Brenner H, Gruber SB, Schoen RE, Berndt SI, et al. A model to determine colorectal cancer risk using common genetic susceptibility loci. Gastroenterology 2015 Jun;148(7):1330-9.e14 Abstract available at
  4. Jenkins MA, Makalic E, Dowty JG, Schmidt DF, Dite GS, MacInnis RJ, et al. Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening. Future Oncol 2016 Feb;12(4):503-13 Abstract available at
  5. Usher-Smith JA, Walter FM, Emery JD, Win AK, Griffin SJ. Risk Prediction Models for Colorectal Cancer: A Systematic Review. Cancer Prev Res (Phila) 2016 Jan;9(1):13-26 Abstract available at