Sporadic colorectal adenomas
More than 70% of colorectal cancers develop from sporadic adenomatous polyps, and postmortem studies have shown the incidence of adenomas to be 30-40% in Western populations. Polyps are asymptomatic in most cases and are often multiple. Flat adenomas, which are more difficult to detect at endoscopy, account for about 10% of all polyps and may have a higher rate of malignant change or may predispose to a more aggressive cancer phenotype.

Recognised familial syndromes account for about 5% of colorectal cancers. The commonest hereditary syndromes are
familial adenomatous polyposis and heredity non-polyposis colon cancer. Patients with these syndromes usually have a
family history of colorectal cancer presenting at an early age. Attenuated familial adenomatous polyposis, juvenile polyposis syndrome, and Peutz-Jeghers syndrome are rarer, mendelian causes of colorectal cancer. In familial adenomatous polyposis (a mendelian dominant disorder with almost complete penetrance) there is a germline mutation in the tumour suppressor gene for adenomatous polyposis coli (APC) on chromosome 5. Heredity non-polyposis colon cancer also shows dominant inheritance, and cancers develop mainly in the proximal colon. Patients with heredity non-polyposis colon cancer show germline mutations in DNA mismatch repair enzymes (which normally remove misincorporated single or multiple nucleotide bases as a result of random errors during recombination or replications). 

Mutations are particularly demonstrable in DNA with multiple microsatellites (“microsatellite instability”).
In addition to the well recognised syndromes described above, clusters of colorectal cancer occur in families much more
often than would be expected by chance. Postulated reasons for this increased risk include “mild” APC and mismatch repair gene mutations, as well as polymorphisms of genes involved in nutrient or carcinogen metabolism.