Summary.-In an experiment involving 950 mice with a normal lifespan of 2-3 years, in laboratory conditions, regular benzpyrene application to the skin was started at 10, 25, 40 or 55 weeks of age. The incidence rate of malignant epithelial tumours among the survivors in each group increased steeply with time. This increase was associated directly with duration of exposure but, given duration, was independent of age at the start of exposure, as were the growth rates of already established tumours.In our experiment, although age per se was irrelevant, the cancer incidence rate increased approximately as a power of the duration of exposure to benzpyrene. This shows that the observed approximate power-law increase of most human adult cancer incidence rates with age could exist merely because age equals duration of exposure to background and spontaneous carcinogenic stimuli. Thus, no intrinsic effects of ageing (such as failing immunological surveillance or age related hormonal changes) whatever need be postulated to explain the vast increases in old age of the incidence rates of such human cancers. This result can greatly simplify speculation about mechanisms of carcinogenesis. THE STRONGEST determinant of cancer incidence rates* in man appears to be age. The probability that a man will develop cancer in the next 5 years is one in 14 if he is 65, but only one in 700 if he is 25 (figures for Birmingham, U.K., from Doll, Muir and Waterhouse, 1970). This relative risk is 50 to one, and differences in cancer incidence rates between young adults and old adults of this order of magnitude are found in many species other than man. In countries with adequate cancer registries, total cancer incidence can be separated into age-specific incidence rates for each site, and between the ages of 25 and 64 many of these separate rates increase approximately as the fourth, fifth or sixth power of age.In this paper, we describe an attempt to determine experimentally whether these marked increases with age arise because unreversed effects of continued exposure to carcinogens accumulate with time or whether they arise because ageing affects the carcinogenic process in other ways.
Local multistage modelThere is evidence that the change from the normal to the cancerous state can take place in distinct " stages ", each with its own causes. It has been shown in the case of mouse skin, for example, that exposure to a tumour initiating stimulus (which may be a subcarcinogenic dose of a skin carcinogen or one or more doses of an incomplete carcinogen, i.e. an agent which by itself is incapable of giving rise to skin cancers) may result in skin cancer formation if these is subsequent exposure to a tumour promoting agent, whereas exposure to * The incidence rate of a cancer at a partictular age is the proportion per unit time of people of that age who develop the cancer of interest.
