Colorectal Cancer

This disease includes cancers in the colon, appendix or rectum. They are mainly adenocarcinomas arising in cells that release mucus. Bowel cancer is the third biggest cause of cancer deaths worldwide but there are large variations in rates. Almost 60% occur in more developed regions, the highest rates being in Europe, North America and Australia/New Zealand, the lowest in Africa and Asia.

New cases/year World 2008: [male: 663,000, female: 571,000];

USA 2011 (est): 101,340; UK 2008: 39,991

Deaths/year  World 2008: 608,000 [male: 320,000, female: 288,000];

USA 2011 (est): 49,380; UK 2008: 16,259

Risk factors Age (most cases occur after the age of 50)

Polyps of the colon

Previous cancers (e.g., breast)

Family history of colon cancer {associated conditions being familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC, also called Lynch syndrome)}

Smoking

Diet (including alcohol and red meat)

Physical inactivity

Inflammatory bowel disease (chronic ulcerative colitis and Crohn’s disease)

Bacterial infection

Symptoms

None that are specific. Blood in stools, symptoms of anaemia, change in bowel habit (constipation or diarrhea), tenesmus (feeling of incomplete emptying on defecation), abdominal pain. The nearer tumour is to the anus, the more likely there will be early symptoms. Metastasis to the liver may cause jaundice. Screening for blood in the feces can now give early tumour detection.

Staging TNM tumour staging system is used.
Major gene mutations

MYC, RAS, ERBB2, P53.

Inherited mutations:

APC (in familial adenomatosis polyposis)

MSH2 (in hereditary nonpolyposis colon cancer)

Treatment

Surgery: curative (early tumours that have not spread too far can be resected), palliative (used to reduce tumour size). Keyhole surgery now often used. Radiotherapy is not routinely used. Chemotherapy: adjuvant, neoadjuvant or palliative.  Drugs used include the combination of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) +/- cetuximab or bevacizumab. Other drugs in use are panitumumab. Bortezomib, oblimersen, gefitinib and erlotinib and topotecan are in clinical trials for treated/untreated metastatic colon cancer.

Intrinsic and acquired drug resistance limits treatment effectiveness.

Side effects

Fatigue, nausea, diarrhoea and numbness in the extremities: hair loss may also occur. General suppression of the immune system and increased infection risk.

Prognosis

Critically dependent of stage at which the cancer is detected: early stage detection has ~5-fold longer survival rates than for late stage detection. The overall USA 5-year relative survival rate is about 60%: for tumours diagnosed when they are still confined to the primary site the rate is 90%: for tumours that have metastasized it is less than 12%.