An efficient primary prevention of cancer requires an integrated approach: Mühlbock memorial lecture

In addition to a wide gradation of levels of exposure to man-made, naturally occurring and endogenous chemicals, to viruses and to radiation, there is a gradation of genetic susceptibility for resistance to the mutagenic and other damaging effects of noxious environmental and endogenous agents. This interplay between environmental and host factors is probably not limited to the early stage of carcinogenesis but extends over the later stages of promotion and progression. The risk of cancer in humans is thus increased by a wide spectrum of factors, which ranges from exposure to an identified agent, such as environmental chemicals or a virus, to culturally determined behaviour, such as age at first pregnancy. We are able today to intervene in some of these factors, while others affect risk by as yet undetermined pathways. Only progress in the understanding of the mechanisms by which these factors act can lead to specific means of cancer prevention. New developments in molecular biology do not invalidate ipso facto all that has been done before. While the new insights about certain aspects of the carcinogenesis process and the new techniques that have been developed in parallel demand that new approaches be explored and developed, there is little justification for downgrading long-term carcinogenicity tests, which provide proven, efficient warning about possible hazards to humans. Support for the maintenance of a programme for testing of environmental chemicals does not mean, however, that one can expect that all or even most of the agents that are carcinogenic to humans will be identified by traditional long-term testing in rodents. Basic and applied research, studies on the mechanisms of carcinogenesis and research on aetiology and prevention are neither opposite nor separate areas of scientific activity. They must be, and indeed are, closely interrelated. The understanding of certain stages of the carcinogenesis process is progressing side by side with the development of much more precise methods than ever existed before for monitoring low doses of exposure at the individual level. While this will be of very considerable help in the conduct of epidemiological investigations, it is clear that the efficacy of primary prevention will increase with, and indeed depend on, understanding of the mechanisms by which a factor or a series of factors contribute to the malignant transformation of cells and/or to their progression to clinical cancer.(ABSTRACT TRUNCATED AT 400 WORDS)