More about the Network
Environmental toxicants play a major role in most diseases of modern industrialised societies, including the two biggest killers, cancer and heart disease. Many factors are involved, but it is the interplay between genes and the environment that is of primary importance in determining an individuals risk of disease. Studies of such gene-environment interactions have emerged as an important component of epidemiological research, and this Network has been set up to establish a European forum for collaboration between the various groups of researchers involved. This will then help with the primary objective of developing a better scientific basis for identifying the groups and types of individual at risk from particular environmental toxicants.
Recent scientific developments have exposed a potential for further research that would improve understanding of gene-environment interactions and their role in human diseases. In addition to cancer and heart disease, new knowledge of the genetic basis for individual differences in metabolism of toxicants has created possibilities for studies focusing on susceptibility to asthma and also neurode generative diseases such as Alzheimers. This Network has been set up to exploit this potential by integrating the different disciplines involved, such as biochemistry, toxicology, epidemiology and public health, and establish better links between previously uncoordinated studies at the national level. Work is also needed to enlarge the existing database on the subject and conduct new research in the hope of resolving contradictory results obtained from previous studies.
The principal objectives are to better understand host factors contributing to varying levels of individual risk, and to estimate more accurately the overall risk of certain exposed sub-populations. These two objectives are closely related, since the high degree of individual variation within some ethnic groups in Europe has made it hard in many cases to resolve differences between one group and another. It has been established for example by Japanese studies that there are considerable differences between Asian and Caucasian populations in the frequencies of polymorphic genes involved in the metabolism of xenobiotica. In Europe by contrast, a project supported by BIOMED found only small variation between groups. This could well be because the strong inter-ethnic variation masked the smaller variation between groups.
Such polymorphisms of metabolic genes are important because although they are less likely to cause cancer than alleles in the so-called "cancer" genes", they are also more commonly occurring in the population. For example 15% to 50% (depending on ethnic group) of the population carry an undesirable genetic polymorphism in one of the enzymes involved in the oxidation metabolism of xenobiotica. People with this polymorphic variety of the gene are more susceptible to cancer when exposed to the relevant toxicant, but otherwise have no greater risk of disease.
Therefore it can be seen that such polymorphisms play a major role in determining the incidence of cancer in modern societies, and a better understanding of the combinations of genetic expressions and the associated biochemistry involved will help identify those individuals and groups most at risk. This is in fact a significant development for epidemiology, since it enables the subjects of surveys to be stratified according to their genotype. It will then be possible to conduct studies where genetic susceptibility is filtered out, making it easier to identify the relationship between environment and various kinds of disease. The use of genetic susceptibility markers for individual environmental toxicants should also make it possible to assess risk more accurately and determine acceptable lev
- To meet this overall objective, the Network is aiming towards the following three related goals:
- To identify the genetic basis for the phenotypic expression of the enzymes involved in detoxification of environmental toxins or protecting the cells against toxicant induced damage.
- Identify new functionally significant genetic polymorphisms in enzymes involved in the protection of cells against toxic compounds.
- Determine the polymorphic distribution of the enzymes in different European populations in order to justify epidemiological meta-analyses to estimate the populations risk imposed by a specific genotype, or more commonly combinations of several genotypes.
These areas of research are still at an early stage, and the ESF Network aims to accelerate progress by bringing together the relevant scientists and practitioners in epidemiology, clinical research and occupational health.
The Network lasts for three years, 1999 - 2001, comprising three workshops, one in each of the years. The first workshop will focus on methodology, the second on analysis of current results pertaining to chronic diseases, and the third on relevant bioethical issues and future developments.
This Network was approved by the ESF Executive Council
in September 1998 for a three-year period.
