Nutritional and molecular markers in cancer prevention
Sheila Bingham
MRC Dunn Human Nutrition Unit and MRC Centre for Nutrition in Cancer Epidemiology Prevention and Survival, University of Cambridge, UK
Secular trends in incidence, international comparisons, migrant studies and studies with twins have all shown a strong environmental cause for most cancers. It has been estimated that at least 30% of cancers, and over 70% for some site specific cancers (such as cancer of the large bowel), could be prevented by diet. This would mean that such cancers are potentially preventable diseases and that dietary factors would be of great importance in public health. Findings from very large molecular epidemiological studies and smaller trials of intermediate risk markers allow some insights into the interaction between diet and the gene variants and dietary mechanisms underlying DNA damage relevant to the development of cancer.
The European Prospective Investigation of Cancer (EPIC) is a prospective study that aims to investigate individual risk of cancer, interaction with biomarkers of cancer risk, and polymorphisms in genes governing nutrient and xenobiotic metabolism. 500,000 men and women have been studied in detail for their dietary habits and their blood samples have been biobanked at –190°C throughout Europe for over 10 years. In colorectal cancer, the first results from the EPIC cohort show strong inverse associations with fibre from food and strong positive effects of red and processed meat. These findings are supported by intervention studies with human volunteers under carefully controlled conditions, showing that haem in red and processed meat enhances endogenous N-nitrosation and the presence of the promutagenic DNA adduct O6-carboxymethyl guanine in exfoliated cells.
Phytoestrogens, found in plants such as soy, have a structural similarity to estradiol, which has prompted hypotheses that they are protective in breast cancer through inhibiting enzymes involved in oestrogen metabolism. In the largest investigation so far conducted, in 2000 women taking part in the EPIC study, there was a significant interaction between isoflavones, sex hormone-binding globulin (SHBG) levels, and SHBG D356N polymorphism (p=0.019). Such interactions may also occur in populations consuming high levels of soy and affect individual risk of cancer development.
