Incidence

Second commonest cause of cancer deaths in both sexes after lung. 30 000 new cases per year in the UK. Increasing incidence with age, > 75 yrs = 300/100 000. Increasing incidence in UK. Colon M = F, rectal M > F, More common in developed countries. Incidence increasing in less-developed nations.

Aetiology

1. Family history: if one first-degree relative, the risk is increased more than two-fold. Two first-degree relatives or one first-degree relative diagnosed < 45 yrs indicates a lifetime risk of death from colorectal cancer of 1 in 6, or 1 in 10, respectively. 5% of colorectal-cancer patients have a genetic syndrome. Familial adenomatous polyposis (FAP) is an autosomal dominant mutation of the APC gene and presents with multiple colonic polyps. Hereditary non-polyposis coli (HNPCC) and Gardner's syndrome are also responsible.

2. Inflammatory bowel disease: ulcerative colitis for over 10 years gives an eight-fold age-related risk.

3. Lifestyle – increased risk with: obesity; smoking; diet – high in processed meats, low in vegetables and fibre, alcohol; reduced exercise; bile salts. Reduced risk with: folic acid, Ca2+, selenium, NSAIDs (including aspirin), HRT.

Pathogenesis

Two-thirds of cancers develop in the colon, the rest in the rectum. Adenomatous polyps have malignant potential via adenoma-carcinoma sequence: have tubular (70%), villous (10%), tubulovillous (20%) morphology. Left-sided cancers tend to be annular, stenosing and more likely to obstruct. Right-sided cancers are sessile and cause occult bleeding. 3% of tumours synchronous, 5–10% metanchronous. Majority are adenocarcinomas. Others: carcinoid, lymphoma, sarcoma. Cancers are graded as well, moderately or poorly differentiated.