The biological revolution - towards a mechanistic understanding of the impact of diet on cancer risk.
There is strong epidemiological evidence to show that differences in diet explain a significant proportion of the variation in cancer incidence worldwide. However, because of the complex nature of eating behaviour and the chemical heterogeneity of foods, it remains very difficult to ascertain which aspects of diet, in what quantities and over what time-frames are responsible for modifying risk. In addition, there are few dietary intervention studies demonstrating reduction in cancer risk. Much faster progress has been made in understanding the biological basis of cancer. It is now clear that damage to the genome resulting in aberrant expression of genes (principally suppression of tumour suppressor genes (TSGs) and inappropriate expression of oncogenes) is fundamental to tumorigenesis. It is also becoming clear that much of the inter-individual variation in cancer experience is due to differences in the amount of damage experienced and/or the capacity to repair that damage. Both of these processes are influenced strongly by dietary factors and by genetic predisposition (polymorphisms in the requisite genes). It is possible that understanding diet:gene interactions in DNA damage and in repair will not only explain much of the inter-individual variation in risk but also offer opportunities to design better dietary intervention studies aimed at chemoprevention. The Human Genome maps and the SNPs databases, together with the rapid development of tools suitable for investigating genetic and epigenetic changes in small tissue biopsies provide the means to begin to test hypotheses about the mechanisms by which diet influences cancer risk directly in human subjects. This is likely to form a significant component of the emerging science of nutrigenomics.
Mathers
John C
JC
Human Nutrition Research Centre, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK. john.mathers@ncl.ac.uk
D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D018890:Chemoprevention; D004260:DNA Repair / Q000235:genetics; D004032:Diet; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk
D016588:Anticarcinogenic Agents; D001241:Aspirin