[Carcinogenesis in humans: a multistage and multifactorial process]

Experimental and epidemiological studies concur to show that carcinogenesis is a multistep process. Over fifty years ago, two steps were identified which were termed initiation and promotion. Initiation is caused by a defect in the cellular genome which is generally provoked by a genotoxic agent. Promotion generally involves epigenetic mechanisms. In those human cancers in which detailed studies have been carried out, the number of steps appears to be generally greater than 2, from 3 to 6. Epidemiologic studies have underlined the long duration and the complexity of human carcinogenesis and show that non gene-toxic agents may play an important role in progression from a premalignant to a fully malignant cell. A large proportion of human cancers have a multifactorial origin. Important advances have been made recently. They have emphasized the usefulness of close cooperation between basic research and epidemiologic studies for the elucidation of the mechanisms involved in the origin of human cancer.