Chemotherapy and Radiotherapy

Oncology for Bowel Cancer.

Doctorate Thesis on Colorectal Cancer

This is the introduction to my thesis on Bowel Cancer, Polyps and Genes.

I hope that the content may help some people rather than the thesis gathering dust.

Please remember that the thesis remains my intellectual property and must not be reproduced in part or as a whole.

Chris Macklin

"There is one thing even more vital to science than intelligent methods; and that is, the sincere desire to find out the truth, whatever it may be."

Charles Sanders Pierce

"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact."

Thomas Huxley

I dedicate this work to the unfaltering support of my wife Lisa and my children, Isobel and Alistair.

My sincerest and heartfelt thanks go to the following people without whom this work would never have been completed:

  • My supervisors Tim Bishop and Paul Finan for all their support and sound advice.
  • The 'FlexiScope Girls', Angela Butler, Joyce Pearson and Sue Corcoran and the staff of the endoscopy unit at Leeds General Infirmary who were so enthusiastic and hard-working.
  • Julie Miller, the FlexiScope trial administrator, who was invaluable and without her I am sure the organisation of the trial would have failed.
  • Juliette Moore, Rupert Gaut and the other scientists and laboratory staff of the Cancer Genetics department of St. James's University Hospital for tolerating a surgeon in their midst.
  • All the staff of the Cancer Research U.K. Genetic Epidemiology department at St. James's University Hospital for their help and support.
  • Jenny Barrett, Faye Turner and Rob Edwards for their amazing ability to instil some statistical understanding to a simple medic.
  • The FlexiScope Trial team headed by Wendy Atkin without whom there would have been no basis for this research.


  • 1.a. The association of diet and cancer.
  • 1.b. Colorectal cancer.
  • 1.c. The aetiology of colorectal cancer and adenomatous polyps.
  • 1.d. Colorectal cancer and screening.

1.a. The Association of Diet and Cancer

Cancers are amongst the commonest causes of death in this country, accounting for about one in every four deaths - almost 130,000 per annum1. The majority of cancer deaths are from tumours found in four principal sites: lung, colorectal, breast and prostate (Figure 1).

Figure 1. Cancer deaths in England and Wales by sex, 1996.

These cancers are common in Western countries but there is a much lower incidence in third world countries (Figure 2). It has been observed that immigrants moving from a low risk area to one of high risk acquire the same risk as the indigenous population within one or two generations suggesting that environmental factors are responsible2.

Figure 2. Geographic variation in the incidence of colon and rectal cancer in men 2.

Tobacco smoking, electromagnetic radiation, environmental chemicals, hormones, bacterial or viral infection, level of physical activity, reproductive and sexual behaviour are thought to be important in the aetiology of cancer at certain sites3. However, it is thought that diet remains the most important factor and it has been estimated that dietary change could result in a reduction of fatal cancers of between 35 and 70%4.

1.b. Colorectal Cancer

1.b.i. Demographics

Colorectal cancer is the second most common cause of death from cancer in the Western world. In 1985, there was estimated to be 677,500 new cases and 394,100 deaths worldwide5,6. In the United Kingdom there is approximately a 4% lifetime risk, 31,000 new cases annually and 16,000 deaths7.

The prevalence increases with age with over 90% of cases occurring after the age of 55 (Table 1). The incidence of colon cancer varies little between the sexes8,9, whereas rectal cancer is twice as common in men as in women2.