ABSTRACT
Colorectal disease is managed by a number of different prophylactic surgical procedures to remove the large bowel, undertaken after the development of polyposis but before progression to cancer. Pathogenic variants in each of the mismatch repair genes are associated with different cancer risks, with the highest colorectal cancer risks in carriers of variants in MLH1 and MSH2, compared to minimal if any increase in colorectal cancer risk in carriers of PMS2 variants, and intermediate risks in MSH6. The combination of early ascertainment, molecular diagnosis and effective prevention and therapy provides direct benefits to the health of those who are affected or at risk, and also allows risks to be reduced or excluded for many family members. Although individually rare, the number of Mendelian tumour syndromes is considerable and there is little doubt that many cases are missed from lack of careful history-taking in what initially may appear to be an ordinary ‘common or garden’ variety of non-familial neoplasm.
