Molecular epidemiology: recent advances and future directions

In 1982 me proposed the concept and a framework for implementing molecular cancer epidemiology. Here, we review progress during the past 17 years in v alidating and applying this approach to cancer prevention. There have been major advances, notably in the understanding of environment-susceptibility interactions in human cancer. However, a review of major findings to date r eveals several urgent research needs to keep pace with the rapid evolution in knowledge of mechanisms in carcinogenesis. Although much valuable progre ss continues to be made in the study of carcinogens that cause direct DNA d amage and are mutagenic, exogenous and endogenous carcinogens can also act by altering gene expression, cell proliferation and differentiation. The me chanisms include aberrant DNA methylation, oxidative damage, effects on met abolism of nitrogen oxide and nitrites, activation of receptors and transcr iption factors, cyclins and other cell cycle proteins. Sensitive, validated biomarkers are needed to detect these mechanisms in small numbers of cells , tissues or fluids. There is also increasing recognition that individual r isk from carcinogen exposure varies as a function of both inherited and acq uired factors. Recent advances in genomics, microassay technologies and inf ormatics hold promise for rapid identification of polymorphic variants or c hanges in expression of genes influencing both response and susceptibility to carcinogens. Another emerging area of molecular epidemiology concerns th e role of nutrition and specific dietary factors (including studies on anti oxidants, energy metabolism, insulin and various growth factors) and the mo dulating effect of genetic polymorphisms. Finally, molecular epidemiology h as enormous potential in cancer prevention through the early identification of 'at risk' populations and the rapid assessment of intervention efficacy . Its success in fully reaching this potential will depend on the applicati on of validated biomarkers, with adherence to sound epidemiologic and ethic al principles.