Cancer originating from the epithelial cells lining the colon or rectum, most commonly an adenocarcinoma; fourth most common cancer in the UK

Aetiology

Risk factors

• Increasing age
• Male gender
• Family history
• Inflammatory bowel disease
• Diet rich in fat and meat and low in fibre
• Smoking, excess alcohol intake
• Diabetes
• Atherosclerotic disease

Genetic associations

• Hereditary nonpolyposis colorectal cancer (HNPCC) - a DNA mismatch repair gene, mutation of the HNPCC gene leads to defects in DNA repair, such as Lynch syndrome
  • Lynch syndrome - late onset, < 100 polys, ascending colon more commonly affected, other cancers associated e.g. uterine, gastric
• Adenomatous polyposis coli (APC) - a tumour suppressor gene, mutation of the APC gene results in growth of adenomatous tissue, such as Familial Adenomatous Polyposis (FAP)
  • FAP - early onset, > 100 polys, 100% risk of developing cancer anywhere in colon, also associated risk of desmoid tumours and thyroid carcinomas

Pathophysiology

• Most colorectal cancers develop via a progression of normal mucosa to colonic adenoma (colorectal ‘polyps’) to invasive adenocarcinoma
• Polyps are often an incidental finding - all visible lesions should be removed by endoscopic mucosal resection as all are premalignant, and patient should undergo lifelong surveillance after resection
• A minimum of 3 separate genetic defects have to occur to allow the progression from adenoma to carcinoma - oncogene activation, loss/mutation of tumour suppressor genes, loss/suppression of genes involved in DNA repair pathway

Clinical features