Cell membrane and dietary fatty acids in colorectal cancer.

The development of colorectal cancer is thought to be a multi-stage process involving a variable interaction between genetic and environmental factors. There is a great deal of epidemiological and experimental evidence which suggests that dietary fat is an environmental influence with a strong aetiological role in colorectal cancer. The mechanism of the promotional effect of dietary fat is unknown, but the cell membrane is a possible target point at which fat might exert an influence. This thesis is concerned with the relationship between dietary fat and cell membrane fatty acids in colorectal cancer. In chapter 1 the literature relating to dietary fat and colorectal cancer is reviewed. Chapters 2 and 3 summarise those facts about cell membrane structure and function and the biochemistry of fatty acids which are relevant to the subsequent work. Chapter 4 describes the methodology used in this work and includes a study of the validity of those methods. The second section of the thesis contains the results of the human studies. Chapter 5 is a discussion of the ways in which dietary fat intake can be assessed in man. Chapters 6 describes a case-control study of erythrocyte fatty acid profiles in human colorectal cancer. Chapter 7 describes an analysis of cell membrane fatty acid profiles in human colonic mucosa and tumours. Section three contains the results of studies using an experimental colorectal tumours model. Chapter 8 describes the development of animal models of colorectal carcinogenesis and addresses the question of their relevance to the human situation. Chapter 9 presents a study of the influence of the type and quantity of dietary fat on the development of experimental colorectal tumours. Chapter 10 concetrates on the cell membrane fatty acid profiles of erythrocytes, colonic mucosa and colorectal tumours in the experimental model. The final section (chapter 11) consists of a summary of the findings of these studies and some concluding remarks including suggestions for further study.