Combining environmental exposure and genetic effect measurements in healthoutcome assessment

The presence of overwhelming difficulties in assessing the extent or even t he presence of a causal association between modern environmental exposures and disease has promoted the use of more complex models in the design of hu man biomonitoring studies. The concatenation of environmental exposure, gen etic effect and individual susceptibility is a key issue in the assessment of risks for populations exposed to environmental pollutants. The use of a biological event laying in the causal pathway from exposure to outcome as s urrogate end-point of disease, can potentially anticipate clinical diagnosi s, offering a number of possibilities for application of preventive measure s. Numerous biomarkers are currently employed to study human populations ex posed to environmental carcinogens, among these, the frequency of chromosom al aberration (CA) in peripheral blood lymphocytes has the most abundant li terature linking a genetic effect with the occurrence of cancer. Findings f rom recent epidemiological studies which have followed-up a large group of healthy subjects screened for CAs have lent further support to the use of c hromosomal breakage as a relevant biomarker of cancer risk. The applicabili ty of surrogate end-points of cancer on an individual basis thus far seems to be limited to few examples. On the other hand, from a public health outl ook, increases in the frequency of surrogate end-points are suggestive of a n increased risk of cancer, and for validated biomarkers such as CAs interv ention policies and actions in exposed populations showing increased freque ncy of these end-points should be always recommended. (C) 1999 Elsevier Sci ence B.V. All rights reserved.