Cancer in Europe imposes a great social and economic burden; in particular the hormonal cancers, breast and prostate, are major causes of death in the EU. It is now clear that a diet high in plant-based foods may offer protection. This project will analyse the effects of two groups of phytoestrogens (isoflavones and lignans), plant compounds with hormonal activity found in food, on the development of breast and prostate cancer. It will study the metabolism of phytoestrogens, individual variation and its influence on cancer risk. This will also include the development of methods for the discovery of new metabolites and for the rapid measurement of bioactive metabolites. This co-ordinated approach using human patients and volunteers, animal models and in vitro techniques will result in in-depth knowledge of the role of these compounds in the development of cancer and enable informed advice to be available in Europe on the beneficial effects of phytoestrogens in the diet.
The overall aim of the proposal is to investigate the preventive role of phytoestrogens (PE) on breast and prostate cancers and to assess the influence, on cancer risk, of interindividual variation in phytoestrogen metabolism, with special emphasis on metabolites generated by the gut microflora.
This will be addressed by the following scientific and technical objectives
- To isolate and identify new metabolites and develop new methods for the rapid measurement of phytoestrogen metabolites
- To define, using the most recent molecular and analytical techniques, the preventive effects of isoflavones and lignans and their metabolites on the stages of development (initiation, promotion, angiogenesis and metastasis) of breast and prostate cancer.
- To assess the potential cancer-preventing effects of PE in specific transgenic and conventional animal models for the development of breast and prostate cancer.
- To evaluate the importance of oestrogens, oestrogen receptors and PE in the aetiology of breast and prostate cancer by analysis of tissues samples from existing, large-scale breast and prostate cancer patient studies
- To evaluate in a human intervention study the impact of individual variation in the metabolism of phytoestrogens on biological parameters indicative of cancer risk
The following major achievements are expected:
- The isolation and identification of new PE metabolites and food precursors of mammalian lignans and development of quantitative methods.
- The development and validation of new, rapid methods for the detection of the isoflavone genistein and the lignan metabolite, enterolactone in urine. Rapid screening methods for plasma equol and O-DMA (another bacterial product) will also be developed. These will be valuable for other research programmes investigating the activities and health benefits of phytoestrogens
- The studies in animal models, human tissues and in vitro systems will provide crucial information on the ability of phytoestrogens and their metabolites to reduce risk of prostate and breast cancer. The studies should reveal the likely stages of the carcinogenic process affected and hence provide information on the value of dietary intervention at early, mid and late stages of cancer.
- The human intervention study is expected to provide crucial information on the importance of the metabolic profile of the individual with respect to the cancer preventing activities of PE and will therefore add to the knowledge necessary to make widespread recommendations to the people of Europe as to dietary changes leading to improved health.
This project will contribute to the further technological development of the field in terms of bioassays and evaluation techniques for assessing cancer risk reduction by dietary components and so help maintain Europe's position at the forefront of the this technology.
The rapid methods for detection of phytoestrogens will have applications for the food industry and for researchers investigating aspects of phytoestrogen metabolism and activity in humans These simple methods will allow an individual to evaluate by her/himself the healthiness of her/his lifestyle.
The successful outcome of the project will also stimulate the awareness of industry and the public of the potential health promoting properties of phytoestrogen-containing foods.