Colorectal cancer 23/11/05. By Chrissie Giles. Reviewed by Jules Harvey and Robin Phillips Colorectal cancer is the third commonest cancer in the UK, only exceeded by lung and breast cancer.

Colorectal cancer (bowel cancer or CRC) is defined as a cancer developing in the colon or rectum (large bowel). It is the second biggest cause of cancer deaths after lung cancer.

Symptoms and diagnosis

The symptoms of colorectal cancer vary with the site and size of the cancer. Many bowel cancer symptoms overlap with more common, non-cancerous conditions, but the importance of any bowel symptoms must be decided by a knowledgeable doctor. Typical symptoms include:

• the passing of blood through the bottom, seen as red or black flecks on/in the faeces
• a persistent change in bowel habits, either to alternating diarrhoea and constipation or to looser stools
• the sensation of the inability to empty your bowels despite passing faeces
• unexplained weight loss
• pallor and tiredness (anaemia).

The diagnosis is suspected following a thorough history and examination by a doctor. The diagnosis is confirmed by a colonoscopy (bendy camera inserted up the bottom), which can look at the whole colon and take biopsies (small samples) if necessary. Genetic testing may be carried out if indicated.

Background: Genetic testing for colorectal cancer

Types and incidence

There are 35 000 cases of colorectal cancer each year in the UK, which can be divided roughly into sporadic, familial and hereditary cases. Most cases (more than 80 per cent) are sporadic and occur in people over 60. Hereditary (inherited) specific gene defects cause less than 10 per cent of cases of colorectal cancer, and around 20 per cent occur in people with a family history of the disease.

Hereditary colorectal cancer

The best-known hereditary colorectal cancer syndromes are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). These syndromes predispose to colorectal cancer at a younger age than normal.

Background: Familial adenomatous polyposis

Background: Hereditary non-polyposis colorectal cancer

FAP causes less than 1 per cent of all colorectal cancer cases and affects around 1 in 7000 people. It is caused by an inherited mutation in the adenomatous polyposis coli (APC) gene. APC is a tumour suppressor gene, involved in regulating cell growth.

HNPCC (also known as Lynch syndrome) affects 1 in 5000 people and first occurs, on average, between the ages of 40 to 50. It is caused by a mutation in one of the DNA mismatch repair (MMR) genes, and accounts for 2 to 5 per cent of colorectal cancer cases.

Familial colorectal cancer

Patients with two or more first-degree (e.g. brothers and sisters) or second-degree (e.g. grandparents) relatives with colorectal cancer are considered to be at an increased risk of the disease. The exact basis is unknown, but familial colorectal cancer is thought to be due to gene mutations or polymorphisms (slight changes in DNA which occur frequently in a population without affecting protein structure), which increase an individual's susceptibility.

For example, a particular APC mutation carried by 6 per cent of people with Ashkenazi Jewish ancestry is seen in 28 per cent of Ashkenazi Jewish colorectal cancer patients with a family history of the disease.

Sporadic colorectal cancer

In most people (i.e. without an inherited mutation predisposing to colorectal cancer or a family history), a series of mutations is needed for colorectal cancer to develop. It often takes many decades for these mutations to accumulate –the majority of colorectal cancer cases occur in the elderly. Mutations in APC are seen in 70 to 80 per cent of sporadic tumours, and often occur early in the development of colorectal cancer.

Other tumour suppressor genes involved in colorectal cancer include p53, which is mutated in 75 per cent of sporadic tumours, and DCC (deleted in colorectal cancer), which is mutated in 70 per cent of colorectal cancers. The K-RAS oncogene is mutated in 50 per cent of all sporadic colorectal cancer cases.

In around 15 per cent of sporadic cases, MMR genes are inactivated.

Causes and prevention

The exact cause of colorectal cancer is not known, although many different genetic and environmental factors have been implicated. If someone has a history of adenomatous polyps or chronic bowel inflammation, the chance of developing colorectal cancer is greater. A previous episode of colorectal cancer also increases the likelihood of the cancer reoccurring.

Smokers have a higher rate of developing colorectal cancer. There have been associations with high fat diets and diets high in red meats. Diets high in fibre and folate (from vegetables) may lower the risk, but any reduction could be due to leading a 'healthier' lifestyle. Leading a healthy lifestyle and being observant of bowel habits are key factors in reducing risk of dying from colorectal cancer.

Treatment

Treatment for colorectal cancer depends on a balance between the location, size and spread of any cancer and the patient's health and choice. In early colorectal cancer, the cancer is removed surgically and the patient is cured by the operation.

In more advanced cases, combined chemotherapy/radiotherapy is sometimes used before surgery to shrink the tumour and make its removal easier/possible. Chemotherapy may also be used after surgery to mop up any remaining cancer cells.

In advanced, incurable colorectal cancer, surgery may be used palliatively to relieve symptoms such as vomiting from bowel obstruction. Palliative chemotherapy may be used (given to try and control symptoms rather than cure), as might palliative radiotherapy.

New molecular therapies are being developed and introduced to target cancerous colorectal cells more specifically. Improvements in chemotherapy drugs have already substantially improved the five-year survival rate for colorectal cancer, with the latest rates approaching 50 per cent. Increased knowledge of the molecular causes of colorectal cancer will lead to new, more effective medications being developed, leading to further increases in survival.

Chrissie Giles is a freelance writer based in London. Dr Jules Harvey and Professor Robin Phillips are at the Colorectal Cancer Research Unit, St Mark's Hospital, Harrow.

Links

Cancer Research UK: About Cancer

CancerBACUP: Cancer of the large bowel

Beating Bowel Cancer

Image credit: Annie Cavanagh. Colour-enhanced image of human colon cancer cells in culture.